[Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] do [Music] [Music] so [Music] good morning and welcome to the day two of the 174th meeting of vaccines a related biological products advisory committee uh i'm mike kuzinski and i along with ma the dfo dr uh prabha atreya and our chair and roboto we will be running today's meeting we look forward to your participation at the public please note this is a live public meeting so we do have presenters and responders and all that from around the world joining us if at any time we run into any technical difficulties we may take a momentary break just to make sure that we can get everything uh squared away so that you don't miss any of the content in today's meeting so that being said i'm going to hand it off to our chair dr monto dr manto are you ready i'm ready and it's my pleasure to open the second day of the 174th meeting of the vaccines and related biological products advisory committee our topic were today and we have a double committee will meet an open session to discuss amending the eua of the modernity covered 19 vaccine to include the prevention of covet 19 infants and children six six months to five years of age and the second topic also to discuss amending the eu a pfizer binding tech covet 19 vaccine to include the prevention of covet 19 in infants and children six months through four years of age uh we next uh will have prabha atreya designated federal officer open the meeting on her side introduce the members and go through the housekeeping issues over to you prava thank you dr dimanto good morning everyone uh this is repava atreya and i'm the designated federal officer for this uh 174th vaccines and related biological products advisory committee meeting and it is my great honor to serve as the dfo for this meeting on behalf of the fda the center for biologics evaluation and research and also the vaccines advisory committee i am very happy to welcome everyone for today's virtual meeting today today the committee will meet in open session to discuss amending the emergency use authorization of the modena covid19 mrna vaccine to include the administration of the primary series to inference and children to six months to five years of age and also to discuss amending the emergency use authorization of the pfizer bionic provide mrna vaccine to include the administration of the primary series to infants and children six months through four years of age today's meeting and the topic were announced in the federal register notice that was published on may 31 2022 at this time i would like to introduce and acknowledge the excellent contributions of the staff and the great team i have in my division in preparing for today's meeting dr susan fedor is my alternate dfo who will read the concepts of interest statement for the public record ms christina wood my backup dfo will be conducting the voting process later today in ancient susan and christina the other staff who contributed significantly are miss joy and bitcoin uh and uh by ms karen thomas miss lisa wheeler and miss viola sampson uh for this meeting i would also like to express our sincere appreciation to mike kahinsky in facilitating today's meeting also our sincere gratitude goes to many fever and fda staff working hard uh behind the scenes trying to ensure that today's virtual meeting will also be a very successful one unlike all the previous vaccines advisory committee meetings please direct any press and or media questions for today's meeting to fda's office software media airport at fta oma fta.hhs.gov the transmission is for today's meeting is uh aura guys uh we'll begin with today's meeting by taking a formal roll call of the committee members and the temporary members when it is your turn please turn on your video camera unmute and state your first and last name and when finished you can turn your camera off so we can proceed to the next person please see the meeting uh member raster slice in which we will begin with the chair uh dr arnald manto dr manto can you start please yes thank you prabha i'm arnold monto i'm at the university of michigan school of public health where i have been involved in research on prevention and control of respiratory infections flu and covid19 for a number of years back to you prabha thank you next eyes dr paula nanciato who will be joining a few minutes later and we can proceed with dr adam berger hi i'm adam berger i'm a geneticist by training i'm also the director of clinical healthcare research policy the national institutes of health where i oversee all of our clinical research and clinical trial policies thanks thank you next doctor hank bernstein good morning i'm hank bernstein i'm a professor of pediatrics at the zuckers school of medicine at hofstra northwell i'm a general pediatrician with special interests in vaccines and public health thank you next week's dr abdullah chatterjee good morning my name is archana chatterjee i have the privilege to serve as the dean of chicago medical school and vice president for medical affairs at roslyn franklin university in north chicago i'm a pediatric infectious diseases specialist with expertise in the field of vaccines thank you thank you next is the captain amanda home good morning i'm amanda cohn i'm a pediatrician and a public health expert at the centers for disease control and prevention with um with expertise in vaccine preventable diseases thanks thank you next week is dr office pal of it good morning i'm paul offit i'm an attending physician in the division of infectious diseases at the children's hospital philadelphia and a professor of pediatrics at the university of pennsylvania school of medicine my area of research interest is mucosal vaccines thank you thank you next is dr steve thanks brava i'm steve pergam i'm adult infectious disease physician at the fred hutchinson cancer center in seattle washington and primarily focus on infections in immunosuppressive patients thank you next is dr j portnoy good morning i'm jay portnoy i'm a professor of pediatrics at the university of missouri kansas city school of medicine i'm an allergist immunologist in the division of allergy and clinical immunology at children's mercy hospital in kansas city thank you next is dr eric rubin dr rubin is running a little late so we're going to move on to the next one brahma okay so next we introduce our temporary voting members dr vavita fuller good morning i'm avida fuller i'm in the microbiology and immunology department at the university of michigan medical school i'm a virologist who studied vowel entry and community engagement thank you next is dr james hilgren good morning i'm james hildreth the president and ceo of harry medical college professor of internal medicine i'm an immunologist and i study viral pathogenesis thank you thank you thank you dr janet lee good morning my name is jeanette lee i'm a professor of biostatistics and a member of the winthrop rockefeller cancer institute at the university of arkansas for medical sciences thank you thank you next is dr offer levy hi uh good morning my name is dr ofer levy i'm a physician scientist and attending physician in pediatric infectious diseases at boston children's hospital where i direct the precision vaccines program bringing precision medicine principles to vaccine research i'm also professor of pediatrics at harvard medical school thank you thank you dr levy next is dr wayne marasco good morning my name is wayne marasco i'm a professor of medicine at the dana-farber cancer institute at harvard medical school i'm a practicing adult infectious disease expert i'm also a research scientist and the work that i specialize in is antiviral immunity and vaccine responses thank you thank you next year's dr premila mcneil good morning i'm pamela mcinnis i am a retired deputy director of the national center for advancing translational sciences one of the u.s national institutes of health institute thank you dr meisner cory meisner i just one sec uh and prava uh we also forgot a member we have to go back to i just thought i'd share that with you okay go ahead doc do i have uh doctor [Music] we are getting a lot of background mike yep i took care of it okay thank you go ahead dr meisner we can't hear you you are muted i think i got it thank you thank you mark and thank you proper and good morning to everyone my name is cody meisner i'm a professor of pediatrics and pediatric infectious disease at tufts university school of medicine the children's hospital will soon close and i will have a new address but i appreciate the opportunity to participate in this meeting this morning thank you thank you next year dr michael nelson thank you dr atreya i'm an allergist immunologist i'm professor of medicine and chief of the division of asthma allergy and immunology at the university of virginia i also serve as the president of the american board of allergy immunology thank you thank you so much dr part rain gold uh good morning my name is art reingold i'm an infectious disease epidemiologist at the school of public health at the university of california berkeley thank you next is dr mark sawyer good morning this is mark sawyer i'm a professor of pediatric infectious disease at university of california san diego and rainy children's hospital my expertise is in the area of public health implementation of vaccine policy thank you dr soy last but not least dr melinda watson good morning i'm melinda wharton i'm an adult infectious disease physician by training and i work in vaccine policy at the centers for disease control and prevention thank you thank you dr wharton uh now i will call the doctor susan to read the concepts of himself statement for the public record thank you we have one more prava we have one more member doctor okay okay okay if she's joined thank you and sorry dr again go ahead please thank you um this is dr haley gans pediatric infectious disease at stanford university relevant to our conversation today i my research focuses on the immune response two vaccines in both immunocompetent and also those children with suppressed immune systems and i sit on many committees looking at adverse um events thank you thank you dr gans okay mike do we have anybody else joining now no we're no we're we're good now thank you okay okay thank you so susan go ahead please and read your concept of inter statement for the public record good morning everyone my name is susan faidor it is my honor and pleasure to serve as the alternate designated federal officer for today's repack meeting thank you for your attention as i proceed with reading the fda conference of interest disclosure statement for the public records the food and drug administration fda is convening virtually today june 15 2022 the 171st meeting of the vaccines and related biological products advisory committee furpac under the authority of the federal advisory committee act taco of 1972 dr arnold monto is serving as the acting voting chair for today's meeting today on june 15 2022 under topic two the committee will need an open session to discuss amending the eua of the moderna covet 19 mrna vaccine to include the administration of the primary theory to infants and children six months through five years of age and to discuss amending the eua of the pfizer bioentech copit 19 mrna vaccine to include the administration of the primary series to infants and children 6 months to 4 years of age this topic is determined to be a particular matter involving specific party pmisb with the exception of industry representative member all standing and temporary voting members of the verpack are appointed special government employees sgs or regular government employees rges from other agencies and are subject to federal conflict of interest laws and regulations the following information on the status of this committee's compliance with federal ethics and conflict of interest laws including but not limited to 18 usc section 208 is being provided to participant participants in today's meeting and to the public related to the discussions of this meeting all members rge and sge consultants of this committee have been screened for potential financial conflicts of interest of their own as well as those imputed to them including those of their spouse or minor children and for the purposes of 18 u.s code 208 their employers these interests may include investment consulting expert witness testimony contracts and grants cooperative research and development agreements c-r-a-d-a-s teaching speaking writing patents and loyalty and primary employment these may include interests that are current or under negotiation fda has determined that all members of this advisory committee both regular and temporary members are in compliance with federal ethics and conflict of interest laws under 18 usd section 208 congress has authorized fda to grant waivers to special government employees and regular government employees who have financial conflicts of interest when it is determined that the agency's need for special government employee services outweigh the potential for a conflict of interest created by the financial interest involved or when the interest of a regular government employee is not so substantial as to be deemed likely to affect the integrity of the services which the government may expect from the employee based on today's agenda and all financial interests reported by committee members and consultants there have been one conflict of interest waiver issued under 18 us code 208 in connection with this meeting we have the following consultants serving as temporary voting members dr ovida fuller dr james hildreth dr jeannette lee dr ofer levy dr wayne marasco dr pamela mckinney dr cody meisner dr michael nelson dr art ryan gold dr mark sawyer and dr melinda orton among these consultants dr james hildreth a special government employee has been issued a waiver for his participation in today's meeting the waiver was posted on the fda website for public disclosure dr paul ananziotto of merck will serve as the industry representative for today's meeting industry representatives are not appointed as special government employees and serve as non-voting members of the committee industry representatives act as a act on behalf of all regulated industry and bring general industry perspective to the committee dr j portnoy is serving as the consumer representative for this committee consumer representatives are appointed special government employees on our screen and cleared prior to their participation in the meeting they are voting members of the committee fda encourages all meeting participants including open public hearing speakers to advise the committee of any financial relationship that they may have with any affected firms its product and if known its direct competitors we would like to remind standing and temporary members that if the discussions involve any other products or firms not already on the agenda for which an fda participant has a personal or imputed financial interest the participants need to inform the dfo and exclude themselves from the discussion and their exclusion will be noted for the record this concludes my reading of the conflicts of interest statement for the public record at this time i would like to hand over the meeting to our chair dr monto thank you so much dr monto thank you and uh now i'd like to call on dr peter marks the director of the center for biological evaluation and research of fda to uh give us his welcome and tell us a little bit about what we are expected to do today thanks very much dr monto first of all uh welcome to people who are tuning in and thank you to both the advisory committee staff the advisors and to the fda staff and to the sponsors as well as open public hearing speakers for joining today we appreciate everyone's participation today we will be considering applications for amending emergency use authorization for both the moderna and pfizer bioentex vaccines to include the younger pediatric populations of uh six through five and six through four years respectively if i could have the slide um mike that i sent you just to remind people of why we're here it's because even though there is a very high thorough prevalence rate of uh the sars coronavirus 2 in uh in the pediatric population there still was during the omicron wave a relatively high rate of hospitalization during this period if one looks at that gray period there at towards the right of this slide that was the omicron period uh and you can see a very sharp wave that rate of hospitalization um actually is uh quite troubling uh and if we compare this to what we see in a terrible influenza season it is worse and the same way as the number of deaths in the zero to four age range during the two years of a pandemic in total um as of may 28th as as we were reminded of yesterday by our cdc colleagues um the total number of deaths as of may 28 was 442 in the uh in the under four age range um that also uh compares uh quite terribly uh to what we've seen with influenza in the past if one goes back to the h1n1 influenza season of 2009-2010 the number of deaths in that age range reported was 78 and we consider that pretty terrible so we are dealing with an issue where i think we have to be careful that we don't become numb to the number of pediatric deaths because of the overwhelming number of older deaths here every life is important and vaccine preventable deaths are ones that we would like to try to do something about we routinely give influenza vaccine across a broad age spectrum in order to help prevent deaths in precisely this kind of manner so i just wanted to set the context here that the intervention we're talking about here is one that is something that we have accepted in the past to try to prevent deaths from influenza here we have a different pathogen but one that has created a lot of havoc just the same and so um as we move today um i think we can kind of help i just wanted to help frame this uh in terms of the magnitude of the issue of a covet 19 in the youngest population granted it's a population that has been much less affected than the older populations particularly the oldest population but one nonetheless uh has also been affected and i think uh for those who have lost children to coven 19 our hearts go out to them because these are each child that's lost is essentially fractures a family so with that said we'll look forward to i think a very good series of presentations some excellent discussion uh and uh wish everyone a very successful meeting today thank you i'll turn it back to dr monto thank you dr marks you've set the scene for what our obligation is today to look at the problem in the youngest of our population and to keep them as protected as possible using uh available vaccines now i'd like to turn the floor over to dr sudakar aguiho crum from fda he is going to walk us through the agenda tell us what we are going to be doing today uh specifically and what the voting questions are going to be this is a little unusual uh kind of meeting where we are looking at two different products and he'll tell us how we're going to be managing going in and out of each with our discussions and then our voting questions uh sudaka thank you very much dr monto um good morning everyone um can you all hear me okay yes sir go ahead okay thanks very much mike um good morning everyone and welcome to the second day of the advisory committee meeting for discussing the pediatric keyways um just a quick thing uh this would be a core presentation uh with dr ramshandanayak um committee chair for pfizer beyond tech with 19 vaccine eua request so i will be co-presenting this um presentation with dr ramsham nayak so with that said um i'm sure and committee chair for modena kobit 19 vaccine eua amendment and um i would like to um begin my talk by thanking the fda eua review committee for modern occupation vaccine supervisors management for all their hard work that went into this and also the advisory committee for their time in this valuable discussion um i would be providing an overview of uh the request from uh madonna on amending their eua for use of modernicobin 19 vaccine acetudo's primary series in children six months through five years of age here is the outline of my talk and then um i will be providing a refresher on the currently available kovit 19 vaccine for prime for use for primary vaccination in children this would be followed by an overview of the request from marina on amending their eua for use of modern akovid19 vaccine as a two dose primary series in children six months through five years of age and the clinical package that supports the ceo request then i would be handing over the presentation to joshua ramachandranayak and he would be talking about the overview of the request from biontech manufacturing gmph on recommending their eua for use of pfizer bay undercover 19 vaccine as a three dose primary series in individuals six months through four years of age and the clinical package that supports the ceo request he will also be providing um a refresher on the statutory requirements for emergency use authorization and dr nayak will um also provide an overview of today's agenda followed by presentation of the voting questions for both the madonna kobe 19 vaccine and the physical undercover dentin vaccine eua request to give an overview of the currently available corporate 19 vaccine for primary vaccination pediatric population paiser biontech covid19 vaccine is available under the eua for use as a two-dose primary series given three weeks apart in individuals five years of age and older kaiser bianca cove with anti-vaccine is also available under the eua for use as a third primary series dose given at least 28 days after the second dose in individuals five years of age and older who have been determined to have certain kinds of amino compromise kubernetes fda approved for use as a two dose primary series in individuals 16 years of age and older and can be used interchangeably with physical biotech 19 vaccine as currently authorized to provide um an overview of the request from modena for amending their ua for use of modern aqua v19 vaccine as a two dose primary series in individuals six through five years of age adena submitted this uh amendment request on april 28 2022 and then the proposed dosing and regimen includes a primary series of two doses 0.25 ml each containing 25 micrograms of mrna command one month apart administered intramuscularly in individuals six months to five years of age the clinical package that supports this eua request includes safety efficacy and immunogenicity data from approximately 1800 vaccine recipients in children 6 to 23 months of age and approximately 3 000 vaccine recipients in children 2 through 5 years of age you will be hearing a breakdown and much detailed presentation on this from both the fda and the sponsors um today i will hand it over to dr ramichandran right now thank you very much thank you dr admitted good morning everyone so my name is uh ram chandra nayak from the division of vaccines and related product applications in the office of vaccines and i am the review committee chair for this era amendment i'm going to provide the background regarding pfizer biotech's eu amendment request for the pfizer by intercoe 19 vaccine for use in children six months through four years of age pizzer submitted this ua amendment request on may 27th the fizer biotech cov19 vaccine is proposed to be administered as a primary series of three doses 0.2 mil each dose containing 3 micrograms mrna first two doses administered three weeks apart followed by a third dose administered at least eight weeks after the second dose administered intramuscularly in individuals six months to four years of age the clinical data package include safety and effectiveness data from about three thousand vaccine recipients six months through four years of age details on this data will be provided in the later presentations by pfizer and the fda as today's meeting is about discussion of amending emergency use authorization from the kovid19 vaccines i'm going to reiterate the statutory requirements for issuing an eoa fda may issue an eua of an unapproved medical product following an eua declaration by the secretary of the u.s department of hhs if the following statutory requirements are met the agent referred to in the eua declaration can cause a serious or life-threatening disease or condition the medical product may be effective to prevent diagnose or treat serious or life-threatening condition caused by the agent the noun and potential benefits of the product outweigh the known and potential risks of the product no adequate approved and available alternative to the product for diagnosing preventing or treating the disease or condition next slide is about the overview of today's agenda after this uh fda introduction moderna will provide the sponsor presentation followed by a fda presentation by dr robin wish on fda review of effectiveness and safety of modern cov19 vaccine in infants and children 6 months through 5 years of age after the 15 minutes break pfizer will provide the sponsored presentation followed by a fda presentation by dr susan walashiam on the fda review of effectiveness and safety of the physical 19 vaccine in infants and children six months to four years of age after the lunch break there will be one hour open public hearing followed by uh additional question and answer for fda and sponsored presenters and committee discussion and voting on uh modern aquarium 19 vaccine and after the break uh additional question and answer for fda and sponsored presentation presenters and committed discussion and voting on fda on pfizer buying the coin 19 vaccine after that the meeting will be uh adjourned next slide is now this is the question to the committee regarding the modern dakota 19 vaccine based on the totality of scientific evidence available to the benefits of the modern koi19 vaccine when administered as a two dose series 20 25 microgram each dose outweigh its risk for use in children six months through five years of age please vote yes or no this is the question to the committee regarding the pfizer buying techcoin19 vaccine based on the totality of the scientific evidence available to the benefits of the pfizer binder cov19 vaccine when administered as a three dose series three microgram each dose outweigh its risk for use in infants and children six months through four years of age please vote yes or no thank you thank you both for your description of our activities today next we go to the moderna presentation and the fda presentation concerning excuse me we had questions and answers i i just realized a few minutes of questions and answers about the substance of our discussions today i mean the process not the substance a few minutes to talk about the process before we uh get into what i was thinking about going to so questions and answers about the process again this is a little unusual because we are switching from one product to the other the reason behind this is that the oral public hearing has to be held at the time it is being held so we're going to be doing this uh switch from one product to the other and going back so we're going to have to pay attention to what we are going to be discussing any questions about the process right now i'm looking to see if i have any hands raised and i do not so uh i was right and going and jumping ahead to the presentations let's do that now i'd like to call on uh dr vinales again who spoke to us yesterday about the other approach to use of the moderna vaccine and she's going to lead as she did yesterday her team dr van als good morning my name is carla vinald and i'm the vice president of regulatory affairs strategy for infectious diseases at moderna thank you again to the fpa and verpack for the opportunity to present today our safety immunogenicity and efficacy data for mrna 1223 the modernize 19 vaccine we are here today requesting emergency use authorization of mrna 1273 as a two-dose primary series for the prevention of covid19 in young children two to five years of age and infants and toddlers six to 23 months of age the proposed to those 25 macrogram primary series is to be administered one month apart the totality of safety immunogenicity and efficacy data from our clinical development program supports that the benefits of mrna 1273 in young children outweigh the known and potential risks mrna 1223 was generally well tolerated and the safety profile is consistent with that observed in older adult age groups no new safety concerns have been identified our pediatric studies were designed to meet fda recommendations for emergency use authorization to infer vaccine effectiveness based on immunogenicity compared to young adults as the efficacy in adults has already been demonstrated in both age groups the core primary immunogenicity objectives were met in addition there was evidence of efficacy against covid19 conferred by mrna 1273 in both age groups and the rates were comparable to the effectiveness observed in adults during the omicron period our clinical trials enrolled more than six thousand six hundred participants across the two age groups and more than five thousand have received at least one dose of mrna 1273 the median duration of follow-up in each study cohort is greater than two months which again meets the requirements outlining the guidance the dose selected met all immunogenicity objectives compared to young adults and vaccine efficacy is consistent with what was observed with adults we have also established plans for extensive follow-up post-authorization to ensure that the long-term safety and effectiveness of mrna 1273 is closely monitored based on this information we will demonstrate today that the benefits of mrna 1273 and infants toddlers and young children outweigh the potential risks here's now the agenda for the rest of our presentation and i'll now turn the presentation over to dr anderson who will review the unmet medical need for covid19 vaccines in young children thank you and good morning my name is dr evan anderson i'm a professor of pediatrics and medicine and a practicing physician at emory university in children's healthcare of atlanta i'm grateful for the opportunity to present today the burden of coven 19 in infants and young children and the need for vaccines this slide lists my conflicts of interests which have not changed since yesterday i've been intricately involved with the clinical trials of coven 19 vaccines including the moderna and pfizer vaccines as a father of four i have a vested personal interest in seeing children protected against covet early in the pandemic there were several common misperceptions about covet 19 in infants and young children and its associated risks as well as the potential needs for vaccination today i will review the data that demonstrate that these were clearly misperceptions first infants and young children do in fact get infected with sariskov2 this slide shows the incidence of sars cov2 infections for 100 000 population over time as reported by cdc infants and young children are represented with the yellow solid line adults and seniors are shown with the gray dashed and solid lines respectively while very few diagnosed cases of sars cov2 infection were observed early in the pandemic beginning with the delta wave and now during the omicron wave we have seen a substantial increase in the number of infections among these children next we also know that these infants and young children do get hospitalized with covid again looking at cpc data we see a substantial increase in the number of hospitalizations during the omicron surge among infants and young children less than five years of age recent data have also shown that there is the substantial burden of hospitalizations in young children this slide shows the outcomes of covet-related hospitalizations roughly one in four infants and young children hospitalized with covet require icu admission in addition while we often hear that hospitalizations among healthy children are uncommon data demonstrate that over 60 percent of children zero to four years of age hospitalized with covet have no underlying medical conditions unfortunately infants and young children can and do die with covid as of june 2nd more than 440 infants and young children aged 0 through 4 have died with covet as documented by cdc this is a tremendous burden of disease 74 deaths in 2020 more than 200 and 2021 and almost 150 in the first five months of 2022.
what is even more striking is when we place the number of dust due to covet into perspective if we think back to the pre-vaccine era for vaccines that we are now routinely using such as rotavirus hepatitis a rubella and varicella the number of deaths that were occurring in children with these pathogens before implementation of routine vaccination were all less than 60 per year flu in the current era ranges up to about 87 deaths per year in children less than 5 years of age for covid since the beginning of the pandemic we've seen 74 to 221 deaths per year among infants and young children zero to four years of age as dr marx has already highlighted what we saw with covet last year alone was more than double the deaths associated with the 2009 h1n1 influenza pandemic this is a tremendous burden having cared for many children children that have been in the icu on ventilators for covid and with misc and having cared for several children that have died of covet we need to be able to prevent covet 19.
finally although the focus is most often on the morbidity and mortality associated with infection covet has dramatically impacted children in many other ways masking and social distancing of young children is difficult almost 60 percent of children 0 to 5 years of age not enrolled in kindergarten are routinely cared for in part by individuals other than their parents such as other family members or by day care frequent unexpected disruptions in child care and schooling have significantly contributed to the daily burden for these families during covet velvet crisis-related family hardships have adversely impacted the well-being of our children finally concerns have arisen regarding the neurodevelopment of children born during the pandemic and increases have been observed in child abuse and mistreatment so in summary infants and young children do get infected with saris cov2 i'd also like to highlight that these infants and children are a continuously renewing population we now have two-year-olds that were born after the onset of the pandemic over three and a half million infants are born each year to the u.s in the u.s and by six months of age these infants are all fully susceptible to coven infants and young children do get hospitalized with covid and the surge in hospitalizations with the emergence of the omicron variant was prominent in our youngest children who have no access to a covet vaccine unfortunately data also show that infants and young children do get hospitalized with covid approximately one in four of these will require icu level care infants and young children do on occasion die with covet in fact we have seen 442 deaths with covet since the start of the pandemic in this age range these deaths far exceed that for many other pathogens for which vaccines are now available and recommended finally these children and their families have been profoundly impacted in many other ways by covet all of this taken together is why a safe and effective vaccine for covet 19 is needed specifically for infants and young children thank you very much for the opportunity to present to you today i will turn the presentation over to dr doss good morning my name is rita das and i'm the vice president of covid19 vaccines at moderna i'm pleased to present the safety immunogenicity and efficacy data from study 204 in young children 6 months through 5 years of age our development program includes more than 5 000 young children who received at least one 25 microgram dose of mrna 1273 overall this represents a substantial pre-licensure safety database in these age groups study 204 was conducted in two parts part one was the open label dose escalation study and it was conducted to select a dose level for further testing in part two which was the placebo-controlled portion of the trial both 25 and 50 micrograms were studied in two to five year old children the 25 microgram dose was chosen for the older children so the 50 microgram then was not investigated in the younger children the 25 microgram dose was chosen for both age groups because it showed an acceptable tolerability profile and demonstrated a high likelihood of meeting the pre-specified immunogenicity success criteria after part 1 was completed a dsmb meeting occurred to ensure the committee's concurrence with the selected dose part 2 randomized children in a 3 to 1 ratio to receive either mrna 1273 or saline placebo the children will be boosted and followed for in an additional 12 months the data we will present today focus on part 2 which evaluated the two dose 25 microgram primary series against placebo the median safety follow-up meets the eua recommendations of at least two months after the final dose the part one cohorts had seven to eight months of follow-up and the part two cohorts had median safety follow-up of two months post-dos two safety endpoints included solicited local and systemic adverse reactions which were collected seven days for post-vaccination all unsolicited events were captured for 28 days after each vaccination an sae medically attended aes and adverse events of special interests were followed throughout the entire study vaccine effectiveness was a primary objective and it was successfully inferred by meeting the predefined immunogenicity criteria which were agreed with the fda there were two non-inferiority criteria first the lower bound of the gmc ratio had to be at least 0.67 and the point estimate had to be at least 0.8 the fda requested that if we selected doses lower than 100 micrograms we ensure that the point estimate of the gmc ratio be at least 1.0 second the lower bound of the difference in zero response rates which were defined as a four-fold rise from baseline titers had to be greater than minus ten percent with a point estimate greater than minus five percent evaluation of efficacy was pre-specified as a secondary objective as in the 301 study there were two case definitions applied the cdc definition which requires one systemic or respiratory symptom and a 301 definition which requires two systemic or a single respiratory symptom both case definition require a nasal swab positive by rtpcr for sars cov2 the cdc case definition was considered primary since children tend to have less severe symptoms of cova than adults turning to results overall the demographics were well balanced between vaccine and placebo in both age groups the mean age in the youngest group was about 11 months and it was three years in the older group gender race and ethnicity also were well balanced next i'll review the safety findings starting with the solicited local reactions in children 2-5 in this figure mrna 1273 is shown in blue and placebo is shown in gray pain was the most common event with similar rates and severity following dose 1 and dose 2.
most local aes including pain were grade 1 to grade 2 with few grade 3 reactions the median duration of local adverse reactions for this age group was 2-3 days looking at infants and toddlers pain was again the most common local adverse reaction although reports of pain in this youngest group were very similar to placebo and much more similar than the older age groups next turning to systemic reaction systemic adverse reactions were evaluated according to age young children's events included fever headache fatigue myalgia arthralgia nausea vomiting and chills for infants and toddlers events included fever irritability and crying sleepiness and loss of appetite headache and fatigue were the most common systemic adverse reactions among children 37 months to 5 years among vaccine recipients systemic adverse reactions were more frequent post-dose 2 compared to post-dose 1 although this difference now was less pronounced than in the older age groups duration was 2-3 days very consistent with the older age groups in this slide we are showing the systemic adverse reactions collected for infants and toddlers on the top are the toddlers age 24 to 36 months and on the bottom are the infants and toddlers aged 6 to 23 months here reporting rates of systemic adverse reactions were similar between dose 1 and dose 2.
also these systemic events were reported at similar rates among vaccine and placebo recipients i will discuss fevers separately since this is a particularly important in the assessment of pediatric vaccines these this slide shows fever by increment among children six months through five years overall fever after any dose occurred in about a quarter of the children the distribution of temperatures was similar between the two h groups reports of fever greater than 40 degrees celsius were rare and over the next few slides i will provide a detailed assessment of all the fevers in this slide we have maximum temperatures post dose 1 and postos2 according to temperature ranges first we look at the fevers in children two to five years we see that fevers occurred more frequently following the second dose it's important to know that note that most reports of fever were less than 39 degrees celsius here are the fevers for infants and toddlers again fevers are reported more commonly postos2 the rates of fever greater than 39 degrees in this youngest age group are very similar to placebo this figure shows fever by day after the second dose in children two to five years of age most evidence of fever occurred within two days following vaccination beyond day two we see that fever rates in the children receiving mrna 1273 are similar to placebo the median duration of fever in this age group was one day it's important to note that this study was conducted during the winter months when respiratory infections are prevalent and this is evidenced by the relatively higher rates of fever in the placebo group as well we see a similar pattern in infants and toddlers with the peak of fever again occurring on days one and two after vaccination on subsequent days fevers look similar among the vaccine and placebo groups the higher background rate of fever is even more prominent in the infants and toddlers there were 15 children with fever greater than 40 degrees celsius in the mrna group and 3 in the placebo group the peak temperature of greater than 40 degrees celsius had a duration of less than one day of the 15 events and vaccine recipients six of the children also had symptoms of concurrent viral infections since febrile seizures can occur in up to five percent of young children next i will talk about the febrile seizures that were reported in children six months to five years there were four episodes of febrile seizures overall in study 204 one was proximal to vaccination and considered related by the investigator this child also had a macular papular rash onset two days after the seizure and then went on to have a subsequent seizure associated with another fever approximately six weeks later the child has remained in the study and received dose 2 of the vaccine without a vet the other three events occurred 10 to 66 days after vaccination and were not considered related by the investigators all three events occurred in children with other symptoms of either concurrent viral infections or one child who had a periodic fever syndrome next i will discuss unsolicited adverse events presented here are the events reported up to 28 days after any injection in children two to five years the incidence of unsolicited aes was similar among vaccine and placebo recipients there were no faes considered to be related by the investigator incidents of maaes were similar and there were no aes which led to discontinuation of the vaccine or from the study after the data cut there was one event of urticaria reported on day one post-vaccination that did lead to discontinuation there were no deaths or adverse events of miss c or myocarditis among the infants and toddlers the incidence of unsolicited aes overall and maaes were again similar among vaccine and placebo recipients there was one sae within 28 days which was considered related to vaccination which i already described in the fever discussion since the data cut of our submissions in late february we pulled the faes from our live database in early may to provide further reassurance of mrna 1273 safety this updated analysis did not identify any new safety signals and there were no saes which were considered by the investigator to be related to vaccination next we'll turn our attention to the immunogenicity data the two co-primary immunogenicity objectives were met for children to two to five years old after the two dose primary series the ratio compared to young adults was 1.01 with a lower bound of 0.88 0 response rates were close to 100 percent in both groups with a difference of minus 0.4 percent and a lower bound of minus two point seven percent next looking at infants and toddlers six to 23 months of age we see again that both co-primary immunogenicity and points were met after receiving the two dose primary series of mrna 1273 the ratio compared to young adults was 1.28 with a lower bound of 1.12 in addition the zero response rate was a hundred percent a group difference of 0.7 and a lower bound of minus 1.0 percent was observed next i'll review the efficacy assessment which was a secondary objective i'd like to highlight that our pediatric studies were conducted an efficacy follow-up was performed throughout a time when the predominant stars cov2 strains were changing and this is important context when interpreting the efficacy results in the two youngest cohorts as shown in this slide the enrollment and efficacy follow-up in young children was conducted during the omicron variant wave the impact of the omicron daily incidence is apparent from the curve shown in red from december 2021 through march 2022 the daily us incidence of stars cov2 infections rose from fewer than 200 000 per day to a peak of 1.4 million cases per day indicating that the stars covey ii epidemiology changed significantly when these youngest cohorts were followed moving now to the efficacy results we took a comprehensive approach to capturing cases all children with symptoms were required were requested to come into the clinic for illness visits where a nasal swab was collected for rtpcr efficacy estimates in the children two to five years were based on 180 cases captured over 71 days post-dos 2.
there was a lower incidence of kovid 19 by both case definitions in children who received vaccine compared to those who received placebo statistically significant efficacy of 36.8 percent was observed using the cdc definition when we get to the 301 case definition we see that the number of cases is reduced and the efficacy is 46.4 percent next looking at efficacy among infants and toddlers six to 23 months efficacy estimates here are made using 85 cases captured over 71 days post dose we again see statistically significant efficacy of 50.6 when using the cdc definition when we get to the 301 definition the point estimate is directionally similar and but the confidence intervals are wider due to the drop in the number of cases to that end at the start of the omicron wave we noticed that parents were reluctant to bring the youngest children into the site for illness visits instead they were calling in results of positive home antigen tests since we captured results from the home antigen test as well we did a sensitivity analysis defining clovid 19 by either positive pcr or home test with the increased number of cases captured the confidence interval narrowed and the point estimates for efficacy were now 53.5 percent and 43.7 percent with confidence intervals excluding zero for context we will now look at real-world effectiveness in adults during the omicron surge to help interpret the vaccine efficacy from our pediatric program presented on the slide on the left are real-world effectiveness data against omicron among adults these data are from our collaboration study with the kaiser permanente health system vaccine effectiveness of mrna 1273 against infection was 44 when the omicron variant was predominant now on the right are the estimates of efficacy from study 204 in infants and young children efficacy of mrna 1273 was consistent with the effectiveness seen in adults while vaccine effectiveness against any infection was lower during omicron we continued to see the benefits of mrna 1273 against hospitalization two doses of mrna 1273 was shown to be 84 effective against hospitalization during the omicron period this is important because we would expect the same level of protection in children given the consistency of the immune response and efficacy with adults study 204 is ongoing and safety follow-up will continue for all participants children will be offered a booster at least four months after the second dose they will be boosted either with mrna 1273 or our bivalent omicron containing vaccine in summary mrna 1273 was well tolerated local and systemic reactions were seen less frequently in these youngest groups solicited adverse reactions were mostly grade one to two and slightly more common after dose two fever was most commonly reported in the first two days after vaccination and resolved in one day no deaths myocarditis pericarditis or ms c were reported among vaccine recipients there was one related sae of fever febrile seizure within 28 days of any vaccination the primary immunogenicity objectives were met two doses of mrna 1273 were shown to be immunogenic gmc's and sewer response rates were non-inferior to young adults vaccine efficacy can therefore be successfully inferred based on immunogenicity in both age groups direct efficacy against covid19 was observed during the omicron period again consistent with the effectiveness observed in adults and now i'll turn the presentation over to dr miller to summarize thank you dr joss good morning to the committee members my name is jacqueline miller and i'm the senior vice president and therapeutic area head for infectious diseases at moderna and i'd like to summarize our presentation for children six months to five years of age dr anderson reviewed a significant unmet medical need remains for pediatric vaccines against sars kovi ii and hospitalizations due to covid19 disease have increased amongst the youngest age cohort during the omicron period of these children approximately one in four will be admitted to the icu since the beginning of the pandemic 442 deaths involving sars kobe 2 have been reported in children up to four years of age and this exceeds the number of deaths due to other vaccine-preventable diseases in their uh respective pre-vaccine eras vaccine effectiveness has been demonstrated in children six months through five years of age via immunobridging the young adult cohort from the 301 study which demonstrated vaccine efficacy against any and severe covid19 disease the immune response has been remarkably consistent across age groups in a two-dose primary series with lower doses administered to younger children this slide depicts the immune responses ranging from young adults to children in all age cohorts and across the pediatric age groups the ratio after the second dose ranged from 1.01 through 1.28 successfully meeting all primary immunogenicity hypotheses additional support for this eua submission was provided through the secondary assessments of efficacy which were comparable with effectiveness in adults for the same variant of concern although we did not observe severe cases of copin 19 in children at the time of the data cut off this consistency leads us to believe that efficacy against severe protection or severe disease will be similar to adults and this will be evaluated in our ongoing post-authorization study we plan to administer booster doses with our omicron containing bivalent vaccine to the six month to five-year-old cohort which will generate the safety and effectiveness data children will be followed for 12 months after boosting the ongoing post-authorization studies we described yesterday will also be extended to the youngest age cohorts so in summary our pediatric development program meets all fda recommendations for eua in children six months to five years of age our clinical trials enrolled more than six thousand six hundred participants across these two age groups and more than five thousand participants have received mrna 1273 with more than two months of follow-up the 25 microgram dose has met all pre-specified immunogenicity objectives and vaccine efficacy is consistent with what was observed with adults during the omicron period allowing the initiation of protection in infants and young children as of six weeks after initiating the vaccination schedule our long-term safety and effectiveness studies will continue to evaluate the impact of mrna 1273 in infants toddlers and young children based on this information we have demonstrated that the benefit risk profile of mrna 1273 is strongly favorable in children six months to five years of age and so we are requesting emergency use authorization of a 25 microgram two dose primary series in children six months to five years of age this proposal is the result of careful dose selection and the optimization of the immunogenicity and reactogenicity profile in this age group and the proposed dosing schedule is consistent with our approved dosing schedule in adults we have heard the feedback from the committee yesterday and want to assure you that all children enrolled in these studies are being boosted and followed for safety immunogenicity and disease incidents for 12 months afterwards and of these a cohort will contain our omicron containing booster since the data over time indicates that omicron represents a step change in the evolution of this virus these booster data will roll out over the summer and we will be submitting them for fda review as soon as possible however as children under four have had the greatest increase in their risk of hospitalization due to covet 19 during the omicron surge initiating this vaccination series now is vital to start protecting children this summer thank you very much to the fda and this committee as well as all of our collaborators and particularly to the children and parents in our summer we heard from one of those parents yesterday and her story was quite compelling i'd be happy to take any questions from you now thank you to the moderna team very clear presentations uh i'd like to ask the committee to come up with some questions on the specifics we're going to have a much broader discussion this afternoon after we hear the fda presentation so this should be mainly for clarification of questions in the short time we have available right now dr ganz thank you very much for that presentation i appreciate also your um giving um doing information about the boosters um i did have a question just um to clarify on maternal antibodies are you collecting at least for the youngest babies at that six month mark um i noticed that in some of the immunogenicity at least in his life that i looked at there were several infants that had pre-existing antibodies and so i'm wondering about are you collecting information on the mother's um immunization status during pregnancy and are you looking at um a pre i'm imagining a pre-vaccine antibody so that's how you're getting the the group that had pre-existing and are we looking for the distinction between infection and maternal antibodies in those so the maternal antibody question continues are those children that are seeing breakthrough disease or are there any differences in that group moving forward no thank you for that question dr gonz um so the uh this particular study did not collect maternal antibodies however we're initiating a study in infants um that are at birth to six months of age and that study called baby cove is initiating now and our intent is to stratify our results uh by immunogenicity all right by biology okay in this group you didn't collect that data even if the mother got immunized or not thank you thank you dr portnoy followed by dr chatterjee coordinator great thank you actually i learned the trick that you hit the raise your hand early and that way you can get your question in in advance exactly i was just wondering about infants and children who in your study who had been previously infected with covet and whether there was any effect of a previous coveted infection on immunogenicity and effectiveness of the vaccine how many of the patients in your study were previously infected and already had some immunity going into the trial yeah so um we actually do have information on those that were previously infected and previously infected is defined as um having uh either a positive rtpcr swab or a um nucleocapsid protein antigen pre-vaccination and can you please put up the slide first for children two to five years of age it's biom4 but the impact that we saw in both children two to four and infants and toddlers six to 23 months of age we did see increases in antibody titers and in fact um evidence of previous infection ad actually led to substantially higher antibody titers and this is really consistent with data that other authors have published suggesting that a combination of a previous omicron infection and vaccination actually leads to the longest protection against further omicron infections and were there any differences in adverse events from the vaccine in those who had previously been infected the the difference was primarily um in um and i'm sorry can you also put up the infants and toddlers please it's i am five slides please thank you uh just to show you those while i talk through the safety data we saw a similar reactogenicity profile but the timing of when those reactions happen is different so the reactions tended to happen more commonly at the higher rate post-dose one versus post-dose two great thank you thank you dr chatterjee followed by dr cohen yes thank you um so i have two questions if i may dr monto the first one is related to slide 39 i believe there was mention made of higher fever noted in some of the participants that had symptoms related to other viral infections potentially other viral infections the question is were these participants tested for other viral infections and do you have those data yeah so um if if the children came into the office the physician may have chosen to test for other viral infections because we were obtaining nasal swabs and not eat swabs we don't have the bio fire results in this younger population as we do in on the older population but this just represents the concurrent symptoms because the parents report uh to the physician all of the aes that are occurring simultaneously we can say that there were multiple symptoms in those six participants okay my second question is with regard to concomitant administration of other vaccines particularly for the six-month-old participants uh were they recipients of other vaccines simultaneously or were those given at a different time yeah so the administration of other vaccines was actually uh given at a separate time and you know the reason for that was when we started this whole endeavor there were actually a number of questions about the appropriate dose the use of the mrna platform and we really felt that it was important to first select the right dose and tease apart and fully describe that reactive to the profile so in the study that we're about to conduct in infants we are going to be looking initially in infants for the right dose without uh concomitant vaccination and then the intent is uh for those um subjects because obviously uh as covid continues with us the renewable cohort is the birth one last question if i may recommend to this is follow up to a very quick one yeah and that is um in the children who received other vaccines were those vaccines given before or after the covet vaccine um i i think it depended on the physician's choice and how they wanted to administer the schedule what we asked was that they separate the vaccinations by at least two weeks for influenza and a month for the other vaccinations thank you thank you dr cohen followed by dr levy thanks dr miller for such a clear presentation uh throughout i um have a question about case ascertainment and i was wondering if you had any data on the percent positives amongst the cases uh the vaccine recipients and placebos and if there was a difference in um the number of uh parents who were bringing their kids in for testing uh between the two groups and uh if there was any um and how often parents were bringing kids in for testing versus how often they were positive for covet yeah um so i should emphasize that parents were really encouraged by the staff to come in and i think that was incredibly important to the investigators in the study they did an amazing job i think at a difficult time um so we did not analyze data based on whether they came in for or did a home test versus an rtpcr what i can show you is the efficacy regardless of symptoms that were reported so that at least gets at some of the milder versus more serious symptoms and so first i'd like to share this slide it's ef45 could you put the slide up please all right so these are the results um in the two to five year olds um and uh as you can see the case split is 120 versus 283 and there was a three to one randomization rate with vaccine effectiveness of 26.9 and a lower limit above zero and i'm going to have to check on the data for the other the other age group and i'll bring that after the break thank you dr levy followed by dr bernstein and unfortunately at that point we're going to have to cut off these questions you'll have a chance later doctor yes thank you for the presentation uh if i understood correctly there were four cases of febrile seizures only one of which was attributed by the investigator as possibly related to the back for that one case can you please let us know more about the current status of that infant and how it played out yeah um so this infant was a 17 month old female she experienced her seizure two days after the first dose her maximum temperature was 103.1 and she was noted after that initial fever a day later to have a macular papular rash on covering her body her temperature actually reached a t-max of 104 on day two so the seizure happened with 103 temperature approximately six hours after her vaccination um she [Music] was treated with ibuprofen and paracetamol was observed in the er and then discharged to home she did actually end up having a second febrile seizure so that happened about six weeks later with with other symptoms of fever respiratory infection and then um she actually did go on to stay in the study receive the second dose without subsequent seizure and um so i think that's um i mean she just continued in the study throughout she's not a discontinuation and the rash would be an unusual finding after the vaccine or you view that as particularly a different i i think it's it's hard to say right fever and rash occurs with the vaccine fever and rash also occurs with spiral syndrome so certainly um something was happening but she was noted to have an o2 stat of 97 she was irritable when she got to the er but but otherwise was okay and what at the time of the seizure she was noted to be limp with no purposeful movements but the seizure was not observed by medical professionals thank you thank you dr bernstein hi thank you very much to you dr miller and your colleagues for very clear presentations my question relates to uh the future studies that you're doing in your discussion about whether these are being termed as boosters or whether this will be a primary series you're talking about a third dose and i think it gets a little bit confusing to the public and to others uh about whether what a primary series is versus a primary series and a so-called booster and i was wondering how you're determining that or why you're labeling it as a booster yeah thank you for that question dr bernstein i know this was a topic that came up yesterday and so i would really like to show the rcc curves from our study in order to maybe discuss that further but while the team pulls up those are our cc curves so it's slide ff4 and ff5 please um the um i think the terminology um you know can call it a primary series you can call it a booster dose i think all of us agree that these children are going to need a third dose at some moment in time but i think the the point i would like to make is by administering these two doses on the schedule that we've shown you begin to see separation of the rcc curve between the mrna 1273 group in red and the placebo grouping group in blue by day 40 in the modified intent to treat cohort so clearly the two dose series is initiating protection early on after the schedule administered at day zero and day 28 and you know certainly appreciate the the points that are being made by the committee and are really committed to not confusing the public but um at this moment our view is it's just critically important to start vaccinating babies so that they can start benefiting from the same protection as other age cohorts and can i also show ff5 please just to be complete in the two different age cohorts okay thank you thank you you see it yep thank you okay did you have anything further to add about the second slide no no just just to show that again um you know by two weeks after the second dose we're beginning to see separation in those two rcc curves which i think ultimately is the objective of initiating immunization in these children thank you and apologies to those who haven't we haven't had time to include in our questions session we'll have much more time later after lunch now we go to the fda presentation the review of effectiveness and safety of modernicovit19 vaccine and infants and children six months through five years of age dr wish thank you good morning i'm robin wish i'm a medical officer in the center for biologics office of vaccines research and review division of vaccines and related products applications at fda i will be presenting fda's review of the effectiveness and safety of the modernity covid19 vaccine in children six months through five years of age submitted under an emergency use authorization amendment i'd like to start off by acknowledging the many contributions of my colleagues in cedar here's the outline of my presentation today i will start with regulatory background and then cover the design of the study submitted to support emergency use authorization for use of the madonna covet 19 vaccine as a two-dose series in children six months through five years of age i will review the part one dose selection data and the part two immunogenicity descriptive efficacy and safety results then i will provide a summary of the planned pharmacovigilance activities and conclude with an overall summary of benefit risk for the six month through five years age group we'll start with background the modernity coded 19 vaccine contains nucleoside modified mrna that encodes for the full length spike protein of stars cov2 encapsulated in lipid particles it was licensed as spike back for individuals 18 years of age and older on january 31st 2022 data included in the eua request for children six months through five years of age were from study p204 a phase 2-3 study with an initial open label dose escalation and hd escalation phase followed by a randomized observer-blind placebo-controlled phase to evaluate the safety reactorgenicity and effectiveness of mrna 1273 vaccine and healthy children 6 months through 11 years of age today i will cover the 6 months through 5 years age groups this pediatric age group blinded follow-up was through the data cut-off of february 21st 2022 data included in the eua request for children six months through five years of age were from study p204 the phase 2 3 study with an initial open label dose escalation and hd escalation phase followed by a randomized observer blind placebo-controlled phase to evaluate the safety reactogenicity and effectiveness excuse me i'm so sorry from all slides this slide provides an overview of the pediatric studies and age groups from 6 months through 17 years of age yesterday the age groups from 6 years through 17 years of age were discussed today i will focus on the age groups from six months to five years of age including approximately 1700 vaccine recipients in the six through 20 months age group which i will refer to as the infant toddler group and three thousand vaccine recipients in the two through five years age group which i will refer to as the preschool group in part one of study p204 the open label dose escalation hd escalation phase enrollment of participants two through five years of age began with a 50 microgram dose level based on the observed rate of solicited adverse reactions in particular the rates of fever after vaccination the study proceeded to enroll the remaining part 1 participants into a lower 25 microgram dose level based on the high rate of solicited adverse reactions in the preschool group at the 15 microgram dose level all part 1 participants in the 6 through 23 months of age group received a 25 microgram dose the immunogenicity results of the 25 microgram dose level in participants in the infant toddler group along with the more tolerable reactogenicity profile of this dose level supported the selection of 25 micrograms as the dose for advancement into part 2 for both age groups part two was the randomized placebo-controlled observer blind evaluation of the selected 25 microgram dose for each age group with just over 4 000 participants randomized in the preschool group and approximately 2 300 participants randomized in the infant toddler group participants were randomized three to one to receive two doses of 25 micrograms of mrna 1273 or placebo given one month apart these are the study objectives and endpoints the safety endpoints included solicited adverse reactions collected for seven days after each vaccination in an e-diary and collection of unsolicited adverse events for 28 days after each dose medically attended adverse events serious adverse events and adverse events of special interest were collected for the entire study duration there was also active monitoring for myocarditis and pericarditis throughout the study as described yesterday using an immunobridging approach gmc's and zero response rates one month post dose ii were compared to young adults 18 through 25 years of age with demonstrated efficacy from study p301 there were also descriptive efficacy endpoints analyzed as secondary endpoints for the immunobridging analysis analyses participants in the per-protocol immunogenicity subset were pcr-negative and or sero-negative for sars-kodi-2 at baseline amino bridging to the young adult cohort can study p-301 in whom vaccine epikc was demonstrated during a time period when the original strain was predominant was based on comparisons of neutralizing antibody responses to the ancestral strain which carries a d614 gene mutation the first co-primary immunogenicity endpoint was gmc ratio of stars cody ii neutralizing concentrations in the specified age group either six to 23 months of age or two to five through five years of age for those in young adults 18 through 25 years of age the success criteria required a lower limit of the two-sided 95 confidence interval for the gmc ratio of greater or equal to 0.67 and a point estimate of the gmc ratio greater or equal to 0.8 the second co-primary immunogenicity endpoint was different from zero response rates between participants of the specified pediatric age group and the young adult age group where zero response was defined as greater than or equal to a four-fold rise from baseline the immunobridging success criteria required a lower limit of the 95 confidence interval for the difference in zero response rates for each of the two pediatric age groups minus the young adult age group of greater or equal to negative 10 percent and a point estimate of difference in serial response rates of greater or equal to negative five percent for your reference this slide again provides the definitions of cdc-divine covin-19 and covid19 as defined in study p301 the two case definitions assessed in the descriptive efficacy analyses in study p204 also for your reference as presented yesterday these are the most pertinent pediatric analysis populations used for evaluations of immunogenicity efficacy and safety this slide provides the follow-up time for study participants calculated from joe's 2 to the cut-off date of february 21st 2022 in the infant toddler group on the top of the slide the median follow-up time from dose 2 was 68 days in the preschool group at the bottom of the slide the median blinded follow-up time from dose 2 was 71 days and the median follow-up time from those two including both blinded and unblinded at follow-up with 74 days the demographics and baseline characteristics of participants in the infant toddler group are displayed in this slide demographic characteristics were comparable between the vaccine and placebo groups the majority of study participants were white and non-hispanic most participants in the study were enrolled in the u.s approximately 20 percent of study participants were obese and approximately six percent had evidence of prior sargoby-2 infection at baseline the demographics and baseline characteristics of participants in the preschool group are displayed here similar to the previous slide demographic characteristics were comparable between the vaccine and placebo groups the majority of study participants were white and non-hispanic and most participants in the study were enrolled in the u.s approximately eleven percent of study participants were obese and approximately nine percent had evidence of prior sarcoby-2 infection at baseline i'll now move on to discussing immunogenicity data shown here is the co-primary endpoint of the ratio of neutralizing antibody gmc's in the infant toddler group compared to young adults at four weeks post-jose ii the study met the pre-specified success criteria of lower bound for gmc ratio greater or equal to 0.67 and point estimate greater or equal to 0.8 with a lower bound of 1.1 and a point estimate of 1.3 this slide shows the co-primary endpoint of difference in zero response rate in the infant toddler group compared to young adults the study met a pre-specified success criteria of lower bound greater or equal to negative 10 and a point estimate greater or equal to negative five percent with a lower bound of negative one and a point estimate of 0.7 the gmc ratio and difference in zero response rates across demographic subgroups were consistent with the results obtained based on the general study population though some of these analyses were limited by small subgroup size results for subgroup analyses that the gmc's in the infant toddler group by baseline sarso v2 status are displayed here the small number of participants with positive baseline sars cody due status in the immunogenicity subset has numerically higher gmc's at day 57 compared to those negative at baseline consistent with the immunogenicity results observed in the 18 through 25 years age group now we move to the preschool group shown here is the co-primary endpoint of the ratio of neutralizing antibody gmc's in the preschool group compared to the young adults at four weeks posters too the study met the pre-specified success criteria of lower bound for gmc ratio greater or equal to 0.67 and point estimate of gmc ratio greater or equal to 0.8 with a lower bound of 0.9 and a point estimate of 1.
this slide shows the co-primary endpoint of difference in zero response rate in the preschool group compared to young adults the study met the pre-specified success criteria of lower bound greater or equal to negative 10 percent and a point estimate greater or equal to negative five percent with a lower bound of negative two point seven and a point estimate of negative zero point four the gmc ratio and difference in sierra response rates across demographic subgroups in this age group were also generally consistent with the results obtained based on the general study population though some of these analyses were also limited by small subgroup size results for subgroup analyses on the gmc's and the children in the preschool group by baseline stars cody2 status are displayed here again participants with positive baseline sars pro v2 status had numerically higher gmc's at day 57 compared to those negative at baseline consistent with immunogenicity results observed in 18 to 25 years of age i'll now move on to the descriptive efficacy data vaccine efficacy was descriptively analyzed as a secondary endpoint in the study with the data cut off of february 21 2022 and during a period when the omicron variant was the predominant circulating strain in the u.s shown here are vaccine efficacy results for first occurrence covid19 starting 14 days after dose 2 based on the cdc and p301 case definitions no severe coveted 19 cases were reported during the study in the infant toddler group among the approximately 6 percent of total study participants with evidence of prior stars kobe 2 infection at baseline one placebo participant and no vaccine participants developed covid19 starting 14 days after dose 2.
analysis of vaccine efficacy including a population of participants both with and without evidence of prior star's cov2 infection or with an unknown baseline status was similar to the efficacy results displayed on this slide these are the vaccine efficacy results for the first occurrence of cova 19 starting 14 days after 2 dose 2 based on the cdc and p301 case definitions for the preschool group in this group there were also no severe covenanting cases reported during the study among the approximately nine percent of total study participants with evidence of prior sars kobe 2 infection at baseline one placebo participant and six vaccine participants developed covid19 starting 14 days after dose 2. analysis of vaccine efficacy including a population of participants with and without evidence of prior stars cov2 or with an unknown baseline status was similar to the efficacy results displayed here i will now move on to the safety data shown here are the frequencies of solicited local reactions in the infant toddler group following each dose local adverse reactions generally occurred more frequently and were more severe after dose 2 compared to after dose 1 although grade 3 events were uncommon the most solicited local adverse reaction was injection site pain solicited local adverse reactions persisting beyond seven days after any dose were reported more frequently in the vaccine group than the placebo group and the majority events were miles this table shows the frequency of solicited systemic reactions after each dose in the same age group the frequencies of systemic reactions were generally comparable across doses and most events were mild to moderate in severity the most common solicited systemic adverse reaction reported in the vaccine group was irritability and crying grade 4 events were rare and only occurred with the adverse reaction fever for oscillated reactions in this age group local and systemic the majority of events had onset within one to three days post-vaccination and resolved within two to three days most events that persisted beyond the seven-day reporting period were mild overall the frequencies of solicited reactions were similar among participants with positive and negative baseline stars cody2 status except for fever which was more common in those who were baseline seropositive now we turn to solicited average reactions in the preschool group in this age group solicited local adverse reactions generally occurred more frequently after dose 2 compared to after dose 1.
adverse local reactions tended to be more severe after dose 2 but grade 3 events again were uncommon the most common solicited local adverse reaction was injection site pain in this age group as well solicited local adverse reactions persisting beyond seven days after any dose were reported more frequently in the vaccine group than in the placebo group the majority of events were mild for the two to five years of age group the solicited systemic reaction terms differed for participants from 24 through 36 months of age and from 37 months through five years of age as shown in the previous presentation this slide shows the systemic reactions in the 24 through 36 months of age subcohort overall the frequency of solicited systemic adverse reactions were comparable across doses with the exception of fever which was reported more frequently after dose 2. the most common solicited systemic adverse reaction reported in the vaccine group was irritability and crying most events were mild to moderate in severity and grade 4 events were rare and only occurred with the adverse reaction fever the next two slides show the systemic reactions in the 37 month through five years of age subcohort solicited systemic adverse reactions generally occurred more frequently and were more severe after dose 2 compared to after dose 1 although most events were mild to moderate in severity the most common solicited systemic adverse reaction reported in the vaccine group was fatigue and as with the other age groups grade four events were rare and only occurred with the adverse reaction fever this slide shows the remaining solicited systemic reactions in the 37 months through five years of age the sub cohort for the entire two through five years age group most local and systemic adverse reactions had onset one to two days post-vaccination and resolved within two days after onset the majority of events that persisted beyond the seven day reporting period were mild as in the infant toddler age group overall the frequencies of solicited reactions were similar among participants with positive and negative baseline sarso b2 status except for fever which was more common in those who were baseline seropositive this table presents the frequencies of unsolicited adverse events in the infant toddler group overall rates of unsolicited adverse reactions were similar across groups unsolicited events reported by at least one percent of participants in the vaccine group and by a higher proportion of the vaccine group compared to the placebo group included injection site reactions and some common childhood illnesses such as ketotis media and group the most commonly reported unsolicited aes among vaccine recipients were upper respiratory infection irritability fever and teething as discussed in yesterday's presentation symptoms of myocarditis and pericarditis were solicited for the duration of the study through scripted safety calls conducted at seven days after each dose and every four weeks thereafter this resulted in enhanced reporting frequency of associated symptoms in study pto 204 compared to those reported in earlier studies and adults in adolescence the same search strategy as described yesterday was also used for evaluation of the safety data set for participants six months through five years of age in the infant toddler group neither the captured event of dyspnia nor the events of irritability and vomiting shown on the slide were identified identified in additional analyses met the cdc criteria for probable or confirmed myocarditis or pericarditis while some respiratory tract related infections were reported with greater frequency in the infant toddler vaccine group than in the placebo group analyses including all respiratory tract related infection preferred terms with and without covering 19 showed generally comparable rates between the two groups as shown in the slide events of proof rsv pneumonia and pneumonia were reported with greater frequency in the vaccine group compared to the placebo group but there was no pattern concerning time to onset or just number for these events and there is not a clear biological mechanism that would explain a causal association for certain respiratory infections but not others overall the frequency and clinical course for these events did not appear unusual given the age group of the study population and the season fall through winter during which the study took place there was also an imbalance in lymphadenopathy related events in the vaccine group compared to the placebo group which were reported by 1.5 percent of vaccine recipients and 0.2 percent of placebo recipients this imbalance is consistent with the imbalance observed for solicited events with axillary or groin swelling and tenderness there were no reported events of anaphylaxis related to study vaccine this table presents the frequencies of unsolicited adverse events in the preschool group overall rates of unsolicited adverse events were similar across groups unsolicited events reported by at least one percent of participants in the preschool vaccine group and by a higher proportion compared to the placebo group included injection site erythema the most commonly reported unsolicited aes among vaccine recipients were upper respiratory tract infection rhinorrhea and cough regarding cardiac events in the preschool group none of the events captured met cdc criteria for probable or confirmed myocarditis or pericarditis and no other events were identified in the additional analyses one participant underwent a valuation by a cardiologist a four-year-old male participant with chest pain five days after dose two that resolved within 30 minutes that evaluation included a physical exam ekg and troponin which were all reported to be normal the majority of events in the study were non-specific in nature and many were associated with concurrent symptoms including respiratory tract infections or allergies in this age group events of pneumonia and rsv infection were reported with greater frequency in the vaccine group and in the placebo group again there was no pattern concerning time to onset or dose number for these events and analyses including all respiratory tract related infection preferred terms with and without covet 19 show generally comparable rates between the two groups overall the frequency and clinical course for these events did not appear unusual given the age group and the study population in the season during which the study took place and again there is not a clear biological mechanism that would explain a causal association for certain respiratory infections but not others events of abdominal pain occurred in less than one percent of participants in each group but were but were reported more frequently in the vaccine group 0.7 percent of participants compared to the placebo group 0.4 percent of participants the three events assessed as related two in the vaccine group and one in the placebo group occurred within two days of vaccination and as discussed yesterday were likely to be manifestations of systemic reactogenicity there was also an imbalance in lymphadenopathy related events which were reported by 0.9 percent of vaccine recipients and less than 0.1 percent of placebo recipients this imbalance is consistent again with the imbalance observed with solicited events with axillary or groin swelling and tenderness there were no reported events of anaphylaxis related to study vaccine in the infant toddler group there were no reported deaths and overall there were few reported serious adverse events or saes 0.9 percent in the vaccine group and 0.2 percent in the placebo group fda assessed all saes in this age court as unrelated with the exception of the events previously discussed of pyrexia and febrile convulsion that occurred within two days of dose one and a one-year-old female participant followed by the occurrence of a macular popular rash that was considered possibly related to study vaccine with a plausible alternate etiology of a viral illness for the two to five to five years of age group there were also no deaths reported and overall there were a few reported saes 0.3 percent in the vaccine group and 0.2 percent in the placebo group most saes were consistent with events typical in this age group and for the season during which the study took place fda agreed with the investigator assessments that none of the reported saes were considered related to study vaccine i'm now going to move on to pharmacovigilance the sponsor submitted a pharmacovigilance plan to monitor safety concerns that could be associated with the madonna coded 19 vaccine they identified anaphylaxis myocarditis and pericarditis as important identified risks and vaccine-associated enhanced disease including vaccine-associated enhanced respiratory disease as important potential risk areas of sponsor identified as missing information included use in pregnancy and lactation vaccine effectiveness long-term safety interaction with other vaccines use in immunocompromised refrail patients or patients with autoimmune inflammatory disorders and use in pediatric individuals less than six months of age pharmacovigilance activities under the eua include adverse event reporting which may come from backing recipients vaccination providers the sponsor or the cdc vsa program both the sponsor and vaccine providers administering madernakovic 19 vaccine must report the following information to theirs serious adverse events irrespective of attribution to vaccination cases of multi-system inflammatory syndrome and cases of covid19 that result in hospitalization or death additionally the sponsor submits reports of myocarditis and pericarditis at 15 days reports to theirs the sponsor will also conduct periodic aggregate review of safety data that i will discuss in an upcoming slide and submit periodic safety reports at monthly intervals for fda review furthermore the sponsor has planned surveillance studies that are summarized on the next slide these are there are four post authorization safety studies of myocarditis and pericarditis shown here including subclinical myocarditis and one post-authorization vaccine effectiveness study that includes individuals 6 months through 17 years of age i've already presented adverse event reporting under eua may come from vaccine recipients vaccination providers or the sponsor reports from vaccine recipients are voluntary while adverse event reporting by vaccination providers and the sponsor is mandatory periodic aggregate safety reports are required to contain a narrative summary and analysis of adverse events submitted during the reporting interval including interval and cumulative counts by age groups special populations and adverse events of special interest a narrative summary and analysis of vaccine administration errors whether or not associated with an adverse event that were identified since the last reporting interval newly identified safety concerns in the interval and actions taken since the last report due to adverse experiences both fda and cdc will take a collaborative and complementary approach on reviewing adverse events in the initial stage of post authorization surveillance fda will individually review all serious adverse events on a daily basis fda will also examine other sources for adverse events such as the literature and will perform data mining to determine if adverse events are disproportionately reported for the candidate vaccine compared to all other vaccines and bears any potential safety signals identified will be investigated and now for a summary of benefits and risks this slide presents a summary of benefits and risks of the madera covid19 vaccine when administered as a two-dose series 25 micrograms each dose in children six months through five years of age known and potential benefits include prevention of symptomatic covid19 based on immunobridging to young adults as well as supportive evidence of vaccine efficacy against symptomatic covit 19 with expected greater effectiveness against more severe disease effectiveness against emerging variants and duration of protection are not yet known known and potential risks include symptoms of reactogenicity potential myocarditis pericarditis and hypersensitivity reactions uncertainties remain regarding adverse reactions that are uncommon or require longer follow-up to be detected the voting question for today regarding the modernicovid19 vaccine for use in children six months or five years of age is following based on the totality of scientific evidence available to the benefits of the majerna covid19 vaccine when administered as a two dose series 25 micrograms each dose outweigh its risks for use in children six months through five years of age and that brings me to the end of my presentation thank you thank you dr wish and you have given us a fair amount of time for you to be questioned because of your succinct uh presentation dr levy is that you raising your hand hi thanks for the excellent presentation i i had a question about what appeared to be an imbalance with respect to rsv infections and pneumonia um and my question to you is i mean you know a priori we might not think that that's possible on the other hand vaccines can have off-target effects effects on innate memory so who knows but just looking at the data is that a statistically significant uh higher rsv and pneumonia signal in the vaccine group and then the left on the far right if you could pull up that slide was a little bit to me because at the same time it said an overall analysis of respiratory infections did not show a difference so so can you talk us through that and let us know what you think or let me go let me go through um i'm going to go through my notes i don't have the slides to pull up individually right a second but so when we did an analysis looking at um all respiratory tract infection preferred terms for the entire study in the 6 to 23 month age group we saw basically the same number of events in each group so 25 21.5 in the vaccine group versus 21.4 in the placebo group in the two to five year age group we saw a similar finding where the rate of all respiratory tract infection preferred terms were similar between the two groups around 17 percent that's for the entire study period when you looked at individual preferred terms under different types of respiratory tract infections there were some imbalances the ones that were pointed out were imbalances where we saw a bit more in the vaccine group compared to the placebo group but there were also other events that were seen more frequently in the placebo recipients as compared to the vaccine recipients i think overall our assessment was was to think that these events were in a low enough percentage of participants and were common events in this age group and at the season um that we we did not consider any of these signals that were picked up i don't know if any uh of my colleagues or madonna would like to to time in and add to that just your colleagues right now it's not confused oh i'd be happy to to add a bit to that so um yes respiratory infections are also something that we looked into as well um with the um imbalances that were noted um established and uh you had a question about statistically significant so i will say that because of the large number of comparisons of discrete medra terms these analyses are descriptive so there's no adjustment made for multiplicity in all of the analyses in the two age groups the other thing i would point out is that there was an imbalance in the other direction for covid19 infections and that really led to the rates of upward respiratory tract infections actually being uh evenly distributed between the two groups so in children who were two to five years of age the rate was 9.2 percent in uh in the placebo group 8.1 percent in the mrna 1273 group and in six to 23 month olds um in the placebo group the rate was 12.2 percent the rate with mrna 1273 was 10.3 percent doctor thank you yeah thank you i i was i was going to make some of the same comments about the statistical considerations for these these numerous um uh preferred term analyses uh but uh you know that being said i i do think that you know if if the vaccine were to be authorized for use in this age group clearly we would we would want to continue looking at uh at these types of events uh in post authorization surveillance we're not uh you know highly concerned about uh a couple of imbalances in one direction and specific events uh uh of infections that are common in this age group we did not see increased severity of these types of infections in the vaccine group compared to the placebo group but it is something that that i think bears keeping an eye on in the post-authorization safety surveillance thank you thank you thank you all dr [Music] meisner followed by dr marasco you dr motto and uh opher i guess got his hands up before i did because i had a question uh similar that is both um slide 37 and side slide 40 uh note that the listed diagnoses are higher um in the mrna 1273 group than they are in the placebo but then the comments they uh seem to say the opposite so that's a little bit confusing um but and i appreciate your explanation and and clarifying that and the reason that it's important i think is because um the effect of covid19 or the sarsko v2 pandemic on other respiratory viruses such as rsv um it's kind of interesting it may the the this appearance of the disease may not have all been due to uh non-pharmacologic interventions there may have been some viral interactions that reduced other viruses such as rsv and influenza so it is an interesting issue as to what's going on here but thank you for the clarification dr marasco followed by dr chatterjee all right yeah thank you very much dr monto and i'd like to address uh a couple of questions to the committee i mean to the fda and i'm happy to have modernist input into this so the viral efficacy vaccine efficacy against uh omicron is lower than one would expect with will hand and this is their first antigenic exposure and i i don't want to be an immunologist associated here but it's pretty clear from influenza data for example that the first virus you get exposed to is going to bios your immune response for the rest of your life it's called immune imprinting so when we're vaccinating with an industrial strain and we're testing against the boosted strain there's an expected um loss of efficacy and this is because this is really antigenic shift not drift like we see in the island of florence this is more like what happened in pandemic 2009 so the real question is are we gathering data on this and my concern is if we just do this blindly and maybe this is the modernist we're just looking at titers really are we going to understand the breadth of the repertoire that is being developed and whether we're biasing or our protection against one lineage against another and that's really the essence of my question it's a matter of you know in 2022 the type of data that we're collecting for these studies this is really more than just zero logic to be able to get to the heart of the problem in the heart of what we're doing thank you thank you you've asked a very broad question that needs a long-term follow-up in general not just in terms of uh this product uh dr bush thank you for that sorry please go ahead i apologize no no no absolutely go ahead i i was i was just going to comment but i think it's a really excellent question and i think it's one that will be evaluated over time as dr monto referred to um so i wanted to mention that we will see the effectiveness or efficacy field efficacy of mrna 1273 against omicron in a study where that we are conducting actually in partnership with south african research council in south africa so really where the omicron variant first emerged and actually now we're boosting health care workers with mrna 1273 during the ba.4b5 period and i think those long-term effectiveness studies are really the best way to understand how a vaccine formulation is going to perform against emerging variants of concern but given that at a certain moment in time what we're left with is being able to look at immune responses i'd like to show if i could slide bf-12 which reflects some of the data that we've been generating with respect to other variants in the youngest age group so um we've been looking actually throughout at neutralizing titers in our older subjects at the moment our omicron neutralization is primarily being performed against the bivalent vaccine that this committee will discuss in two weeks but what we do have are some binding data with respect to the various variants and i see the computers thinking about it there we go so this complicated slide but what you see in this uh four different rows are the um ms so a multiplex system binding antibody to um the uh four uh key variants so first starting with the ancestral strain in the bavarian and in blue the delta variant and then in purple the omicron variant and then moving left to right what you see are they why don't you wait until breeze you can see what see if we're not seeing it yet oh i apologize i apologize i thought i'm able to see it so i thought you were as well no i'm we're not i have it okay but we can see it okay you can see okay go ahead yeah arnold some of us can see it thank you okay okay not able okay good doctor just to clarify this is with the omicron vaccine just just a cloud no no with this is with mrna 1273 these are samples studies that you are doing today um and so we have tested um children uh or sierra from children um for all of the different variants because as you mentioned while omicron is our particular consideration today um i i think that it's likely that this virus continues to evolve over time so you see different variants in different colors the omicron is in purple at the bottom of the slide and the dotted line in each of the graphs represents the limit of detection of the assay and so in all cases what we're seeing is an increase against the variance of concern i think the question around what is the right way to prime individuals is a very good one and it's why we are going to start a primary vaccination study with the bivalent to see if the primary series looks different in terms of antibodies that are generated versus the original mrna 1273 vaccine thank you and i assume you have some neutralization uh essays on some of them at least i don't want you to pretend about that you're you're following up okay dr wish do you have anything uh in addition to i'd add beyond that thank you okay uh dr chatterjee followed by dr kim thank you dr monto i have two questions i have the suspicion that the sponsor might need to weigh in but the first one is on slide 29 um on dr wish's presentation and this was with regard to the local reactions in the younger cohort i was wondering how pain was determined in pre-verbal children was that inferred in some way or how would they know if a six-month-old had pain um the the parents and caregivers of the children provided e-diaries i would have to again refer to the sponsor to see if they can give a more precise explanation of how parents assess that okay i would think it would be gas yeah so um just to make sure i understood the question the question is how we understand um how pain is measured in six-month-old children yes some yeah children yeah because you're absolutely right obviously they can't complain about pain but it has to do with the parents assessment of the level of discomfort for example when the child's arm or leg um is moved are they crying um so it to to maybe give you the different great grades um where maybe um there's you know a reaction when things are touched moving to grade two that they're crying when their limb is moving then significant pain at rest preventing just abnormally what the child's doing is grade three okay thank you doctor kim doctor followed by dr hildreth well thank you very much dr monto and and that was a terrific presentation dr uh dr wish i have a question on your slide number 26 and 27 um and this i think this uh this question would all would also apply to our vagina colleagues the efficacy study for the infants and toddlers uh was fifty percent uh using the cdc definition and um and using the the study definition from for modern art 301 was 31 and on the following slide 27 uh looking at things for this for the preschool age group uh we're talking uh 36 percent and 46 percent uh respect respectively uh for cdc and and study now the uh there's a there's an overlap between uh between these two uh uh efficacy results but uh but it's interesting that the cdc definition and the p uh and the study 301 definition that basically are are inversely related between the uh between the infant toddler group and the preschool group and i and having looked at the look at the data much more closely to what if any uh actual attributes have you seen in the findings that might explain this this opposite direction of action efficacy findings between these two uh age groups and and perhaps our bengali county colleagues can add to that other than small numbers and chance please uh please please uh dr wish sure thank you for that so yes if you look at the tune up like dr monte is where i'm thinking as well um you can see you know the p301 definition is a more stringent definition of coping 19 disease and so the numbers are smaller for both age groups for those diagnosed with p301 definition as compared to the cdc definition if you look at the vaccine efficacy for the younger six to 23 months that the confidence interval is much wider and crosses zero so you know it's hard to interpret interpret the reliability of that vaccine efficacy for that population with that definition um but we did see the trend that of course there were fewer cases with the p301 definition um and and it's just it's difficult to tell because of the small case numbers using that more stringent definition in this population but i'd refer to modernist they want to add to that thank you uh let's let's go ahead so we can get to the bottom of our list of questioners dr hildreth followed by dr fuller who will have the last question uh thank you dr monto and thank you dr wish and dr benalls for your great presentations my question is related to the just prior question that was asked the data shows that the efficacy for the toddlers and the infants have much lower efficacy than the six to 11 year olds but the data you've shown us show that they all have about the same geometric titers for neutralization so is there a disconnect there that you can help me understand the neutralizing antibody titers are clearly the same but the efficacy is not so i just would like it out we understand that thank you for that question um the one thing i can say is that um in the time period when the infants and toddlers or the younger pediatric population were being evaluated was during ombrecon whereas i believe the six to 11 year old age group was evaluated during the time of the delta surge um so there is that that difference in um my period as far as efficacy of the vaccine against the various variants again so mosul type virus neutralization assay did you do a side by side comparison of omicron and delta to confirm that i would have to refer to majerna for that okay a very a quick response we're going to have time to go into this in detail later on so please quick response because i'd like to get to dr fuller sure sure um so um great question and mentioned we're in the process of generating the neutralization data against omicron and the other variants with respect to the youngest kids we did review a slide yesterday um bf11 in the older children um just to show you how it looked across age groups versus the ancestral strain so can i have the slide up please bf11 okay let's do it quickly just real quick i promise okay um just to answer to dr hilder's question which is are we looking into omicron we continue to look at neutralization titers across age groups and also as new variants emerge okay thank you thank you dr fuller final question before the break yes so you mentioned that you looked at obesity as a underlying factor did you look at things between the two and six year olds like sickle cell or asthma that might be underlying conditions and the results of the vaccine in those yes there were the underlying comorbidities that were looked at including obesity were also respiratory chronic respiratory conditions including asthma and cardiac conditions the numbers of children in each of those subgroups were very small so it was hard to come to conclusions about about differences given the very small numbers but things like sickle cell or or uh juvenile diabetes that can be diagnosed early they did not look at it there are no i'm sorry i apologize diabetes was included i don't recall seeing sickle cell disease in those baseline comorbidities they're i'm i'm not sure of that um i can pull up i know in the briefing document i have there is a table of baseline comorbidities and we'll show you that i can't recall if there were if there were cases of diabetes um they were very very small it wouldn't be on these slides it's in the in the briefing document i can find that information and get back to you thank you okay thank you all uh it's time for the break and we will resume at 11 eastern which is about 13 minutes from now 11 00 at eastern missouri all right thank you arnold and yes please take us to break [Music] [Music] so [Music] [Music] do [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] do [Music] [Music] do [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] do [Music] [Music] [Music] all right and welcome back from that break uh let's just we'll keep the ball rolling here and i'm going to hand it back to our chair dr monto thank you mike and we are now switching to the bnt 162b2 visor biontech covet 19 vaccine and the request is for emergency use authorization for use in infants and children six months through four years of age and we're going to hear from dr gruber of the senior vice president at pfizer take it away bill good morning on behalf of pfizer and biontech it is my pleasure to share data supporting the bnt 162 b2 request for emergency use authorization in individuals six months through four years of age my name is bill gruber and i head the vaccine clinical research and development group advisor today's agenda covers the topics shown here with specific attention to coverage of the clinical safety immunogenicity and efficacy data along with the assessment of benefit risk there is a clear unmet medical need in children six months to less than five years of age for a safe and effective covet 19 vaccine and you've heard this discussed at length over the past two days i'm going to summarize and in a single slide less than five-year-olds are currently the only pediatric group for whom vaccine is not available severe covet 19 occurs in children less than five years of age and as of may 2022 there were over forty five thousand hospitalizations with roughly half of these hospitalizations due to omicron with a high number of icu admissions and deaths the burden is comparable to influenza as you heard from dr marx for which children are routinely immunized severe covet 19 outcomes are unpredictable and can occur in healthy children 64 of hospitalizations in children less than five years of age occur in those without comorbidities covet 19 can cause additional long-term sequelae in children three to six percent of children report continued symptoms for greater than 12 weeks and importantly the pandemic adversely impacts development and psychosocial well-being whether or not a child is isolated because of covet-19 infection because of the social distancing and other requirements that limit in-person schooling and other social interactions the need for three mrna vaccine doses to protect against omicron related covit 19 is clear omicron is significantly more transmissible than prior variants in adult populations two doses of the current mrna covet 19 vaccines do not adequately neutralize omicron a third dose increases breadth of coverage and can neutralize omicron more effectively real world data show that a third dose significantly improves protection against omicron related symptomatic disease and severe illness given the high prevalence of omicron and the emerging evidence that three doses of mrna vaccine are needed against omicron we studied three doses of bmt162b2 in children six months through less than five years of age pfizer biontech is seeking emergency use authorization of the three microgram dose level of the vaccine in children six months through four years of age the proposed indication is for active immunization to prevent covet 19 caused by sars coronavirus 2 in individuals 6 months through 4 years of age the vaccine would be administered intramuscularly as three doses of 0.2 milliliters each two doses would be administered three weeks apart followed by a third dose at least eight weeks after the second dose the three microgram dose was chosen as it had the right balance between immune response and a satisfactory reactogenicity profile i'm now going to share with you the clinical data that supports emergency use authorization here's the study overview information which should be familiar to you but now focuses on children six months to less than five years of age to select the appropriate pediatric dose levels for infants toddlers and very young children we carefully evaluated multiple dose levels in phase one we began in five to eleven year olds before progressing to sixty four participants in the six month through four-year-old age group to achieve the right balance and safety profile and immune response these pediatric groups represent a more vulnerable population so it is particularly important to minimize reactions including fever while achieving an immune response likely to provide protection against covid19 we were therefore very deliberate in dose ranging we found that nearly nineteen percent of two to less than five-year-olds who received the ten microgram dose developed fevers after the first and second dose and one third of those fevers were severe we were concerned that the frequency and severity of fever seen after the 10 microgram dose would likely further increase in the infant and toddler group of six months to less than two years and could be poorly accepted by parents reducing adherence to the primary three dose series in contrast the three microgram dose had a much better tolerability profile combined with comparable immune responses to the sars coronavirus 2 reference strain therefore the 3 microgram dose level was advanced into phase 2 3 in the country shown to infer efficacy in the pediatric population the pivotal study immunologic non-inferiority to a 16 to 25 year old population for whom efficacy was established was assessed in addition to safety to satisfy emergency use authorization immune response criteria although not required for eua approval covid19 surveillance was conducted permitting an early evaluation of vaccine efficacy this study schema should also be familiar to you children were administered two doses as shown at the top 21 days apart and then a third dose was administered at least 60 days later follow up for reactions adverse events antibody response and surveillance are parallel to that described for older children current follow-up includes one month postos-3 serology and efficacy to the data cutoff of april the 29th safety data as of the april 29th cutoff date follow all safety data that i will present is in the blinded placebo control follow-up period i will first discuss the safety data into the less than five-year-olds and then the six-month to less than two-year-olds demographics in the two to less than five-year-old age group are balanced between vaccine and placebo groups whether gender race or ethnicity note at the bottom of the table the 12.7 to 13.7 of participants had evidence of prior our current sars corona virus 2 infection at the time of the first dose approximately 12 to 14 percent of participants had underlying comorbidities including obesity here are the tolerability data for two to less than five years of age group care providers for participants with and without cryosaurus coronavirus to infection at baseline reported local reactions by maximum severity within 7 days after each dose these include redness swelling and pain at the injection site color-coded as shown local reactions were mostly mild to moderate in severity somewhat higher in the vaccine recipients compared to placebo recipients and did not show an increase from dose two to dose three local reactions were higher or similar in frequency and severity and those with evidence of prior sars coronavirus to infection at baseline and all within a well tolerated range there were no grade four reactions care providers for participants to the less than five years of age with and without prior sars coronavirus 2 infection at baseline reported systemic events shown in this table let me orient you to the slide dose 1 those 2 and dose 3 are shown in each of the rows with the color-coded rating scales as shown placebo recipients are paired up with the vaccine recipients for each of the symptoms shown systemic symptoms solicited by electronic diary were mostly mild to moderate fever fatigue or other symptom rates were remarkably similar to those seen in placebo recipients and much lower than those in older age groups immunized with higher dose levels fever rates are comparable or lower than other childhood vaccines the low incidence of fever observed after each vaccine dose generally peaked by day two and declined by day four only three or less than 0.2 percent of bnt 162 b2 participants reported fever greater than 40 degrees centigrade after dose 1 or dose 2 starting on day four day day two day four day six with all returning to normal uh six to seven days after the dose one of these had a presentation suggestive of a viral example none of these required hospitalization and all resolved quickly systemic symptoms were higher or similar in frequency and severity and those with evidence of prior stars coronavirus to infection at baseline and all within a well tolerated range this highly favorable tolerability profile for the pfizer biontech vaccine should be reassuring to parents and care providers in the two to less than five-year-old age group blind and safety follow-up occurred from the time of dose 2 to dose 3 are cut off date for a median of 4.3 months and for dose 3 to the cutoff date for a median of 1.4 months as a reminder randomization was in a 2 1 ratio unsolicited adverse events are shown here by proportion reporting at least one adverse event with vaccine recipients in blue and placebo recipients in red overall unsolicited adverse events during the blinded part of the study to data cut off and two to less than five-year-olds were comparable between vaccine and placebo recipients and evaluation during the unblinded period did not change this assessment related adverse events serious adverse events and withdrawals were infrequent and comparable between vaccine and placebo groups most saes were gastrointestinal or respiratory infection illnesses with no imbalance between groups three subjects or 0.2 percent in the bnt 162 b2 group withdrew from the study due to adverse events pyrexia considered related status epilepsy epilepticus considered unrelated and urticaria considered unrelated one participant in the placebo group withdrew to facial swelling and rash considered related further details are in the briefing document there were no deaths reported in this age group adverse events occurring in one percent or more participants by system organ class were comparable between vaccine and placebo recipients from dose one to cut off whether for any adverse events or the subcategories shown lymphadenopathy in the bnt 162 b2 group at the 3 microgram dose was 0.1 this was a lower frequency of lymphadenopathy than that reported in older children and adults i'm now going to turn attention to the safety evaluation in six months to less than two-year-olds the demographics are shown here again with balance between the vaccine and placebo groups related to gender race or ethnicity as shown at the bottom of the table between 7.6 and 7.4 percent of participants had evidence of prior or current sars coronavirus ii infection at the time of dose one four percent to six percent of individuals enrolled in the trial had underlying comorbidities reports of local reactions by maximum severity are shown in this figure in the same way that they were shown for the older population local reactions in the six month to less than two-year-old group with and without prior sars coronavirus ii infection were mild to moderate with incidents somewhat higher in vaccine recipients local reactions were somewhat higher or similar in frequency and severity and those with evidence of prior stars corona virus to infection at baseline and all within a well tolerated range there were no grade four events and frequency remained relatively the same after each dose again consistent with a very well tolerated vaccine caregivers and participants reported e diary systemic events by maximum severity within seven days in this age group with or without prior stars coronavirus ii infection note that the symptoms shown in this age group differ somewhat in terms of how they are captured because of age so shown here are fever decreased appetite drowsiness and irritability all of which were mostly mild to moderate and similar to placebo rates fever rates were once again comparable or lower than those observed in older children and adults fever rates are comparable or lower than fever rates of other childhood vaccines these were usually occurred by day two and declined by at least day four or sooner after each dosing with vaccine beaver greater than 40 degrees centigrade was reported by only three recipients or less than 0.1 percent for each dose starting on day one day two or day three with all returning to normal by at least five to six days after the dose two of whom had a concurrent viral infection one fever greater than 40 degrees centigrade was reported by a placebo recipient after the first dose none of these required hospitalization and all resolved quickly given the similarity in reactions much of the febrile illness in both groups may reflect viral infections common in this age group systemic symptoms were somewhat higher or similar in frequency and severity and those with evidence of prior stars for virus ii infection at baseline and all within a well tolerated range again the overall incidence and low severity of systemic symptoms speaks to a favorable tolerability profile for the pfizer biotech vaccine that should be reassuring to parents and care providers safety follow-up including binded follow-up from the time of dose 2 to dose 3 or the cutoff date was for a median of 6.3 months and from dose 3 to the cut-off date was a median of 1.3 months unsolicited adverse events shown here are similar to the pattern i've described to you in the older age group overall unsolicited adverse events were comparable to pain vaccine and placebo recipients related aes saes withdrawals were infrequent and comparable between vaccine and placebo groups most saes were gastrointestinal or respiratory infection illnesses three participants or 0.3 percent in the bnt 162 b2 group withdrew from the study due to adverse events all related to due to a fever greater than 40 degrees celsius one of which had a viral exam and then that was considered unrelated one participant withdrew due to a generalized rash on the face and trunk and further details of these events are included in your briefing document there were no deaths reported in this age group once again adverse events rates in this group occurring in one percent or more participants by system organ class were comparable between vaccine and placebo recipients from dose one to cut off lymphadenopathy was reported in only two percent participants or 0.2 percent in the bnt 162 b2 group and none in the placebo group the frequency of reported lymphadenopathy is lower than that reported in older children and adults few adverse events of special interests were recorded and were of similar incidents to placebo fda adverse events of special interests are reported here for both age groups predominant categories were potential angioedema and hypersensitivity comprising mainly urticarias and rashes for cdc defined adverse events of special interests no vaccine-related anaphylaxis no myocarditis no pericarditis no bell's palsy and no misc was observed the carefully selected dose level of three micrograms for the bnt162b2 vaccine was shown to have an excellent safety profile and was well tolerated in infants toddlers and very young children vaccine reactions were mostly mild to moderate and short-lived with systemic in reactions comparable to placebo reactions were comparable after dose one two and three the unsolicited adverse event profile mostly reflected reactogenicity or common childhood illnesses the safe and well tolerated vaccine profile of the carefully chosen three microgram dose should reassure parents and providers specifically the vaccine provides high protection against omicron if all three diseases are received and i'll share that with you shortly the low incidence of fever and systemic reactions similar to those of placebo recipients should encourage vaccine adherence for each of the three doses i will now describe immune responses in children less than five years of age demonstration of non-inferior immune response in children less than five years of age after three doses compared to immune responses in 16 to 25 year olds after two doses was judged by the fda as sufficient to meet immunologic success criteria for emergency use authorization immunobridging criteria in the two to less than five-year-olds were met for both gmr and seroresponse which infers vaccine effectiveness in this age group shown here are the saris chromositis coronavirus ii neutralization assay titers to the reference strain postos3 and children to the less than five years of age in the light blue after three doses compared to those 16 to 25 years of age in the darker blue after two doses with the geometric mean ratio shown on the right hand side the median dosing time between dose 2 and dose 3 was 10.7 weeks the geometric mean ratio observed was 1.30 and importantly had a lower bound of 1.13 thus well above the success criteria required by the fda this was also true for the immune abridging criterion relying on zero response i draw your attention to the difference in percent responders on the right hand side which is one point two percent between the two to less than five-year-olds and the sixteen to twenty-five-year-olds with a lower bound of minus one point five percent which is well above the minus ten percent non-inferiority success criterion i now turn to the six month to less than two-year-olds immunobridging criteria are met for both gmr and seroresponse which infers vaccine effectiveness in this age group as well the median dosing time between dose 2 and dose 3 was 12.9 weeks the scheme is the same and i draw your attention to the right hand side of the slide where the geometric mean response was 1.19 with a lower bound of one well above the 0.67 required success criteria immunobridging criteria were met for the sierra response with 100 of children less than two years of age responding and a difference in percent of responders of one point two percent with a lower bound of minus three point four again well above the minus ten percent required success criterion so for both younger children as well as the older children immunobridging criteria were met given that most current covent 19 cases are caused by omicron we also evaluated the ability of two and three dose immune syrup from six months to less than five-year-olds to neutralize omicron compared to sarah from adults in this graph the older comparator group is a 24 to 74 year old adult sentinel cohort from the leicester trial that has been used throughout development to evaluate antibody response to emerging variants immune responses to omicron shown in pink were compared to those of the reference back screen strain shown in blue using a plaque reduction neutralization assay gmts are shown on the y-axis and age groups are shown left to right as you can see we see comparable immune responses across all three age groups to the reference strain and omicron however as reported by several groups homotron responses after only two doses are low and uniformly so across the pediatric and adult groups low omicron neutralization titers after two doses seem to correlate with lower efficacy after two vaccine doses for omicron however this picture changes when serum samples after three doses are being evaluated in this data set an adult comparator group was used that received the third dose at a similar time interval after the second dose as the pediatric roof at about 11 to 13 weeks antibody responses were measured using a fluorescent focus neutralization assay this data has been submitted to the fda and as a supplement to the briefing document left to right for six months or less than two-year-olds and two to less than five-year-olds the omicron specific neutralization titers after three doses are far higher than those on the prior slide after two doses and the omicron specific titers are very similar across age groups most importantly the pediatric group titers are essentially the same as in the adult group predicting that similar efficacy as shown in adults could likely be observed for the six months to less than five-year-old age group i will shortly share with you descriptive data showing observed post-dose 3 efficacy matching this prediction so here are the immunogenicity conclusions in six months to less than five-year-olds all immunobridging criteria post-dose 3 and young children required for an emergency use authorization were met for both age groups inferring effectiveness omicron neutralization titles were low after two doses for pediatric and adult cohorts but increased substantially after a third dose in the six months to less than five-year-olds to similar levels observed in adults thus has been as it as has been observed in other populations a third dose is required also for the six months of less than five years of age group to ensure more robust protection against covert night team due to omicron so what have we learned from the adult and pediatric experience about the potential for bnt 162 b2 efficacy against covet 19.
here is a summary of this of observed efficacy data in the blind and follow-up period that while not required for an eua supports the importance of a third vaccine dose to protect children less than five years of age against omicron just as a third dose is important to protect older children and adults against omicron it's important to note that nucleic acid amplification testing was defined either based on a central laboratory determination or an acceptable test in a local laboratory for all cases in addition it's important to remember that the follow-up for this population after the second dose was greater than four months for less for two to less than five-year-olds and greater than six months for six months to less than two-year-olds details including 95 percent confidence intervals are in your briefing document and the 95 percent confidence intervals for omicron after the third dose are shown on the next slide efficacy is shown on the x on the y axis and by age six months to less than five years on the left with the age groups displayed progressively to the right efficacy against the delta variant is shown in blue and efficacy against the omicron variant is shown in pink please note that the delta surge ended prior to the third dose so no children were exposed to delta after the third dose marked as na you can see efficacy against delta postos2 in the evaluable population without evidence of infection prior to seven days post dose two of seventy point two percent was observed in six months to less than five year olds shown on the left and moving left to right fifty six percent and two to less than five year olds and ninety one point six in six months so less than two-year-olds this is consistent with a high level of efficacy against delta after two doses of vaccine and comparable to that observed in older children and adults the emergence of omicron presents a new challenge shown in pink on the left you can see that for children six months to less than five years of age post those two efficacy was 21.8 percent in the six-month the less than five-year-old age group and correspondingly as shown for the other subgroups this is consistent with the poor antibody response after the second dose that i shared with you and is consistent with lower efficacy against omicron and older children and adults after two doses compared to other variants like delta now look what happens after the third dose cases post those three in this clinical study occurred after february 7 2022 and were confirmed to be omicron this confirmatory data is being submitted to the fda efficacy in the all available population against omicron rises to 80.3 percent overall and correspondingly so for the respective age subgroups this descriptive observed efficacy well exceeds the original fda guidance for an efficacy point estimate of at least 50 percent this is consistent with the higher antibody response seen after the third dose against omicron like that of older children and adults and consistent with corresponding higher efficacy in older children and adults after a third dose against omicron this table displays details of the high descriptive eighty percent efficacy observed after the third dose during a period when omicron was predominant note that the large n in this table represents the population followed during the placebo-controlled blinded period of the trial up to the data cut off of april the 29th and note that the trial was randomized two to one vaccine to placebo whether we're talking about the sixth month to less than five-year-olds or for the subgroups high efficacy was observed in the course of this trial with 80.3 percent efficacy shown in the overall age group with a 95 percent confidence interval lower bound of 13.9 percent 82.3 and 75.5 percent efficacy were observed in the respective age subgroups with larger confidence intervals of course because these subgroups are smaller and individually have a smaller number of cases so what can we conclude about efficacy is as demonstrated in other pediatric and adult age groups two doses of bnt 162b2 are protective against variants of concern such as delta but do not provide adequate protection against omicron as demonstrated in other pediatric and adult age groups a third dose is necessary to provide high protection against omicron in addition to six months of follow-up as part of the current clinical trial ongoing and active pharmacovigilance and pharmacoepidemiology will continue with a focus on any expanded pediatric populations receiving vaccine these include the pharmacoepidemiology studies for ages six months and up and you can see that five studies are noted here no myocarditis was noted in the clinical trial of children less than five years of age and this rare event does appear appear to be less of a risk for five to eleven year olds however evaluation for such a rare event will be expanded into this age group as part of routine pharmacovigilance proactive risk mitigation will continue including labeling educational material and bile differentiation with the maroon top and pharmacovigilance will continue as shown and can be consistent with pharmacovigilance in older children and adults already underway the potential benefits of vaccinating children six months to less than five years of age outweigh the known potential risk this age group of six months to less than five years of age is currently unprotected protection against covet 19 is critical particularly in light of the unpredictability of potential new waves and emergence of new variants of concern available safety immunogenicity and efficacy information support a highly favorable benefit risk profile for administration of three doses of bnt-162b2 at three micrograms to children less than five years of age overall given the favorable benefit risk profile pfizer biontech requests emergency use authorization of bnt 162b2 for active immunization of individuals six months through four years of age administered intramuscularly as a three dose series and biontech wish to thank the clinical trial participants sites investigators cro our partners and their staff and the fda guidance to assess this urgent medical need i and my pfizer colleagues will now be happy to take questions thank you dr gruber uh dr pergam has is next uh followed by dr gangs dr paragon uh thanks dr ruber for that uh presentation um i was curious um we haven't seen much of the data related to the dose the dose finding in the initial phase one study i'm curious if you can describe a little bit about whether there was a difference in immunogenicity between the three microgram versus 10 microgram is there a dose dependency in that in that particular in that particular comparison i'm just curious based on on differences in dosing of the vaccine and thanks for that question obviously as they said we paid strict attention to defining just the right dose that gave us the appropriate immune response after three doses um there are really two lines of evidence that support the basis for the dosing decision one is the reactogenicity that i already shared with you but the second one is really if we can bring up the slide uh with the pink bars that speaks to the omicron response you may recall that while that's coming up that we made decisions at the time of phase one based on comparisons to an adult population that gave us reassurance that for the reference train we were likely to meet non-inferiority right because that's the criteria for licensure but in addition to that if we can put slide three up this is really the most compelling information that having chose the three microgram dose and giving it is three successive doses we now essentially uh nearly equal the sort of response that one sees in adults for which we know we have good protection against omicron so i think that confirms for us with the reactogenicity profile that i shared you and this finding uh that this is the right dose to provide protection and again although it's you know it's early the 80 efficacy that we're seeing essentially matches what you would expect based on this type of response okay again mike just as a piece of clarification um did you see did you see a difference in that three microgram versus 10 microgram in terms of antibody responses it's just a clarification question the nature of the antibiotic responses were both above the responses that we saw in adults but combined with the reactogenicity profile and knowing that for the reference strain we would be in a position to potentially meet non-inferiority we chose that strain because we again we chose that that dose because we again um wanted to be confident that the vaccine would be accepted obviously we already know that in older individuals you know thirty percent of children are not getting the vaccine a lot could be a lot of reasons for that but one of them is the reactogenicity so combined with that and again the data that i'm showing you here it seems pretty clear that the three microgram dose is the is the right dose and and followed by the obviously the phase three data that we have on reactions which are very comparable to what we see in placebo recipients okay thank you uh moving on dr gans followed by dr portnoy thank you for that presentation i had a follow-up question maybe to steve's question regarding the dosing and i was looking at the slightly lower immune responses in the two to five year old to the current dosing and i'm just wondering are there additional studies that actually may be looking at differing dosing and splitting these groups as we know it's a very large immunologic group and there may be some nuances to how the toddlers or the pre-preschool group is different than the infant group so that's one question um i would also like you to be talk a little bit about your breakthrough disease and see if there was any um differences in the severity of disease and those who had received vaccine versus those who were in the placebo group i realized hospitalization wasn't something so that's not really what i'm asking i'm asking about the disease profiles in those two groups let me take your first question first about the nature of splitting the roofs i think the approach that we've taken is very consistent with every other age group in terms of dealing with the pediatric population so for 12 to 17 year olds they get a 30 microgram dose for the five to 11 year olds they get 10 and four now the six month to um five-year-olds they receive three micrograms and again you know based on what we saw in in the older children where we had 19 percent severe fevers uh in the phase one group we really don't feel uh comfortable expanding on that dose and we don't need to because we now see with the three dose series which i think most people uh now agree and we heard from paul offit yesterday the importance of a third dose in an omicron era that this is the right dose to immunize children to protect against omicron for the second piece the nature of severity of the illness we've actually included in your briefing document and there was really no difference if we looked at all the cases so i'm talking about based on the number of symptoms that they had uh in terms of breakthrough compared to placebo whether it was you know one two three or more symptoms there really was not a dime's worth of difference uh between the the respective groups between those that break through that receive vaccine versus placebo so that gave us confidence in that larger you know sort of population of cases that we have that that that does not appear to be an issue and it also doesn't seem to if the disease is the same in the placebo group um it didn't show a necessary advantage of the vaccine i guess was what i guess the advantage of the vaccine is you're preventing the infection in the first place right so you know that's the big advantage right and but the good news is it doesn't seem to make the disease worse if in fact you've received the vaccine and i think that's an important thing and why we looked at it thank you uh dr portnoy followed by dr cohen thank you i guess i'm a little bit confused about uh this uh dosing in terms of micrograms because ear dosing is 3 micrograms the modernity dosing is 25 micrograms clearly we're thinking in terms of micrograms the way we would think of proteins as a way of inducing an immune response and yet the purpose of mrna is to induce protein production so is your pro is your mrna just more efficient at making cells produce protein or how should we think of micrograms in terms of the amount of spike protein that's produced by the cells can you kind of clarify that yeah i'll leave to modernity to describe the nature of how they address their vaccine dosage but i think obviously we don't have a complete understanding of the nature of the way that the vaccine works in terms of reducing immune response so you have to go by the results and the results are that in the setting of giving a three microgram dose we had low reactivity compared to placebo and after a third dose just as in adults at higher doses we're getting an immune response that's comparable it may well be the children we've seen certainly in you know that we're able to go down to a lower dose in children and the expectation is perhaps they have a more robust response that seems to be the case based on giving a 10 microgram goes to 5 to 11's and 3 micrograms to younger but have you ever measured the amount of protein that's produced as a result of the mrna and how many cells are producing it and how persistent that production is for a given microgram of mri that is that's a pretty broad question but yeah i think that that's obviously you know an interesting question to better understand the mechanism and i would say it's somewhat academic in the setting of what we're trying to achieve here in terms of getting an immune response and a safety profile it's satisfactory but worthwhile for people to pursue thank you let me just say dr janssen the head of vaccine research and development would like to make a comment about that last question very brief thank you bill um i think one one important uh consideration for the the answer to the question that was just posed is that the two mrna vaccines are not created equal they actually very different vaccine they use the same platform they have different formulations and so i think that's important to uh to recognize and the second piece is that we of course have optimized the vaccine for optimal expression of the antigens and and if you ask the question is there logic number of protein molecules expressed in the cells the answers yes thank you thank you both so dr cohen final question thank you so i have a um this is maybe a multi-part question but i'm i'm wondering how you can be so sure uh of your both your immunity immunogenicity and ve estimates in the setting of the requested interval that you've requested between two and three doses is actually different than any of the um it is actually very different than the median in which your recipients received that third dose so how can you be sure that they would have a similar response eight weeks after the first dose and that sort of goes back to you know this time period between the second dose where there appears to be very little to no effectiveness um and the third dose would would essentially mean that these kids would not be protected at all for an additional eight weeks so i'm trying to sort through both you know you looked at effectiveness uh in kids who were vaccinated a longer period after that second dose and if you have any kids or any data on immunogenicity after eight weeks so thanks for the question i think where we take a great deal of comfort is sort of comparing like to like so the nature of comparing this 11 to 13 week comparison in the older adult population to the immune response we're seeing in the in the younger sort of translates to the likelihood that you're going to get similar efficacy with that interval likewise i think it's reasonable to assume that the if the interval were lower you would compare to what we saw in adults as well i think there were a fair number of individuals that did actually get the vaccine in the 8 to 13 week period that are obviously being monitored as part of our ongoing assessment of efficacy and perhaps we'll learn something from that uh particularly as time goes on and we have longer follow-up so but to clarify we don't actually have do we have data on adults that are immunocompetent immunocompetent that were vaccinated eight weeks after their second dose we um in terms of data in terms of eight weeks [Music] i'm not sure that we actually have a day that we've analyzed uh at eight weeks so essentially what you're saying and i i hear your confidence which is great but what you're asking for this eight-week interval is not the same and can't be compared to adults or to the kids to many of the kids who are in your study i guess you know what has to and and dr cohen i appreciate the question i think what has to be balanced here is a reasonable expectation that we'll have some level of efficacy certainly seeing that we have 80 percent at 11 to 13 weeks and the need to get children vaccinated as quickly as possible to essentially achieve that efficacy that was part of the reason as you know that for our primary series we looked at 21 days we wanted to narrow that interval what was reasonably possible to have enough maturation of immune response that you get a good you know response after the second dose if we lengthen out now the period of time after the third dose and we're all hearing and you know the data supports that you need a third dose for omicron you're you know essentially trading off a theoretical issue that maybe i'm not going to get quite as good efficacy for the notion of a child you know having that period of exposure before they can get that third dose so i think that is the sort of thing that has to be weighed okay thank you dr gruber we're moving on now to the fda presentation on the efficacy and safety of the pfizer biotech vaccine dr susan willersheim in the clinical review branch at d.a will be giving us the presentation dr waller shouts so much dr monto can you hear me okay we can thank you and mike if you could add my notes that would be great fantastic i see them now thank you so much i'm susan wallersheim a medical officer in the division of vaccines and related products applications at the fda i will be presenting the fda's review of the effectiveness and safety of the pfizer biontech covid19 vaccine in children six months to four years of age submitted under an emergency youth authorization amendment or eua and i'd like to start by acknowledging so many contributions from so many colleagues across the fda thanks so much to outline my presentation for you i will start by providing the regulatory background of the product and the study design followed by a brief review of the phase 1 dose selection then the phase 2 3 immunogenicity descriptive efficacy and safety results followed by the pharmacovigilance plan and a summary of the benefits and risks for this product to begin the pfizer beyond tech covid19 vaccine is based on the sars cov2 spike glycoprotein s antigen derived from the wuhan strain encoded by rna and formulated in lipid particles this slide shows a summary of the various age groups dose levels regimens and current authorizations and approvals for the primary series of this product the eua under discussion today is listed at the bottom of the slide and is intended to support use of a three dose primary series of the phaser biotech covid19 vaccine at the three microgram mrna dose level the fda has issued related euas previously as listed at age appropriate dose levels as a two dose primary series and a third primary series dose for certain populations in august of 2021 the pfizer biantec covid19 vaccine was approved under biologics license application under the proprietary name community for use in individuals 16 years of age and older and this slide presents some key features of the two prior pediatric euas issued for the pfizer biantec covid19 vaccine in may of 2021 for adolescents 12 through 15 years of age and october 2021 for children 5 through 11 years of age the eua issued for children 5 to 11 years of age is for the 10 microgram dose level while the 30 microgram dose level is authorized for use in adolescents 12 through 15 years of age data from clinical studies submitted to support the euas for both age groups included similar safety endpoint immunobridging approaches and descriptive efficacy analyses the safety database for vaccine recipients and percentage of participants with two months or more of follow-up at the time of each eua data cutoff are shown and as you will see from the rest of the presentation this eua request for children six months to four years of age has similar features now we'll move on to the study design study c4591007 is an ongoing phase one two three randomized blinded placebo-controlled study to evaluate the safety and effectiveness of bnt 162 b2 in children 6 months through 11 years of age and was the basis for the eua issued for children 5 through 11 years of age the focus of this eoa request is the remaining participants six months through four years of age also enrolled in the study my slides are moving sorry okay so for phase one a two dose primary series of the vaccine was evaluated in u.s children who were not at high risk for staroscopy to exposure did not have medical conditions that represented risk factors for severe cobit 19 and did not have evidence of prior star's cov2 infection those levels of 3 and 10 micrograms are evaluated in an open label manner for each age group starting with the older age group and based upon safety evaluation and recommendation by the internal review committee selection of the three microgram dose level for both age groups was driven by reactogenicity and supported by immunogenicity obtained at 7 days post dose 2.
phase 2 3 of study c4591007 is being conducted in the united states finland poland and spain this portion of the study did not exclude children with a history of sars covi2 infection children with known hiv hepatitis b hepatitis c or stable pre-existing chronic disease participants were randomized two to one to receive two doses of vaccine or saline placebo three weeks apart and immunogenicity was assessed in a subset of participants at one month post dose 2 to infer effectiveness as the primary endpoint following analysis of the post-dose ii safety and effectiveness data a third primary series dose was added for participants six months through four years of age at least eight weeks after dose two in protocol amendment six approximately 4 500 total participants have been enrolled at the time of this data cut off and enrollment is ongoing to expand the safety database immunogenicity at one month postdos 3 was assessed in a subset of participants and efficacy data was obtained through continuous surveillance for potential cases of covid19 there were two circumstances for participants to be unblinded during the study and the first was if they turned five years of age and became eligible to receive vaccine as available under the eua from october of 2021 and the second was the planned unblinding at the six-month post-dose ii visit in the original protocol prior to the addition of the third dose to the primary series the subjects randomized prior to protocol amendment 6 were unblinded six months post dose 2 and offered vaccine if they originally received placebo the first placebo crossover occurred in november of 2021.
subjects randomized after implementation of the protocol amendment 6 will be unblinded at their 6-month postdos 3 visit and offered vaccine if they originally received placebo the notable implications of unblinding during this study are that the descriptive efficacy analyses include only blinded participants however the safety analyses do include all participants who received any study intervention regardless of those who are blinded or unblinded this slide outlines the study objectives and an endpoint immunogenicity was evaluated one month post dose 3 and analyses were conducted by age group with two primary endpoints of geometric mean titers and zero response rates tested sequentially efficacy was evaluated with continuous surveillance for potential cases of covid19 and safety data was collected from all participants who received study intervention as follows safety analyses included solicited local and systemic reactions or reactogenicity for seven days after each vaccination via e-diary unsolicited adverse events were collected within 30 minutes after each dose which were considered immediate adverse events and from dose 1 through 1 month after each dose serious adverse events will be collected from dose 1 through 6 months after dose 3 or the data cut off the effectiveness of the pfizer beyond tech covid19 vaccine is being inferred by comparing neutralizing antibody responses against the wuhan like strain obtained one month host dose 3 and the pediatric age group separately compared to a subset of participants 16 through 25 years of age enrolled in the vaccine efficacy study c4591001 in which the overall vaccine efficacy was 91.2 and participants 16 through 55 years of age participants in each immunogenic analysis population did not have evidence of prior source cov2 infection immunobridging endpoints and statistical success criteria will be discussed in the next two slides this slide shows the first immunobridging analysis based on geometric mean titer or gmt thesaurus cov2 neutralizing antibody titers obtained one month post-primary series are being compared and participants without evidence of prior stars cov2 infection the gmt ratio compares each pediatric age group to the young adult age group from study c4591001 with sex with success criteria that the lower limit of the two-sided 95 confidence interval is greater than 0.67 and the point estimate of the gmt ratio is greater than or equal to 1.
The second immunobridging analysis is based on zero response rate which is defined as the percentage of participants with a greater than or equal to fourfold rise from baseline the success criteria is a lower limit of the 95 percent confidence interval for the difference in sierra response rates being greater or equal to negative 10 both immunobridging analyses had to meet success criteria for overall success of the primary endpoint and this slide provides the case definitions for protocol-defined symptomatic covid19 and severe covet-19 used for the vaccine efficacy analyses symptomatic covid19 was defined as the presence of at least one of the lifted symptoms on the left side of the slide as well as a confirmed sars kovi-2 pcr positive test during or within four days of the symptomatic period severe covet 19 includes the symptomatic covid19 case definition with at least one of the listed criteria on the right side of the slide such as abnormal vital signs various levels of respiratory and systemic illness icu admission or death vaccine efficacy was a secondary objective planned after 21 confirmed cases had been accrued across both age groups and conditional unsuccessful immunobridging this slide shows the various analysis populations for each age group for which you will see results today the numbers of vaccine and placebo recipients listed reflects the two to one randomization and the first row shows the total numbers of participants who received any dose of study intervention there are notably smaller numbers of participants in the dose 3 efficacy analysis population shown in the bottom row of the slide due to unblinding and attrition for the 6 through 23 month age group a total of 715 original vaccine recipients and 377 original placebo recipients were unblinded during the study conduct and for the two to four year age group a total of 842 original vaccine recipients and 424 original placebo recipients were unblinded this slide presents the demographics and baseline characteristics of subjects 6 through 23 months of age these demographics are also comparable to the immunogenicity and efficacy populations which are subsets of this overall safety population the treatment groups were balanced in terms of demographics and baseline characteristics the median age was 16 months seven to eight percent were positive at baseline for sars kobe 2 status the majority of subjects were white and 14 identified as hispanic participants were enrolled in four countries the us spain finland and poland with the u.s contributing most participants comorbidities were reported in four to six percent of participants including asthma cardiovascular disease and congenital heart disease and this slide shows the demographics of the safety population for the older age group which was generally comparable to the younger age group and as a reminder the immunogenicity and efficacy populations are also subsets of this over safety overall safety population the treatment groups were balanced in terms of demographics and baseline characteristics the median age was three years comorbidities were reported in 12 to 14 percent of participants including asthma neurologic disorders and congenital heart disease obesity was present in approximately seven percent and of note there were no hiv positive subjects enrolled into the study for these age groups will now move on to the immunogenicity data here you see the results for the gmt primary endpoint in children 6 through 23 months of age among participants in the evaluable immunogenicity population without prior evidence of sars kobe 2 infection the ratio of gmts was 1.19 which met the success criteria for immunobridging as the lower bound of the two-sided 95 confidence interval for the ratio was greater than 0.67 and the point estimate was greater than or equal to 1.
results for subgroup analyses of the gmts in children 6 to 23 months of age by baseline sars cov2 status are displayed here the definition of baseline star's cov22 status is based on results of the n binding antibody and saros covi2 pcr tests obtained prior to dose 1. participants with positive baseline sars cov2 status had numerically higher gmts compared to those negative at baseline which is consistent with immunogenicity results observed in the older age group the numbers of baseline positive participants though was limited to six in the vaccine group and eight in the placebo group the baseline negative group may also include participants that became infected after dose one and before one month post dose three of note results for the serial response rate immunobridging endpoint in children 6 through 23 months of age are displayed here among participants in the evaluable immunogenicity population without evidence of sars kobe 2 infection the percent difference in zero response rates was 1.2 which meant the suspects the success criteria as the lower bound of the two-sided ninety-five percent confidence interval was greater than negative ten percent and here we'll move on to the older age group the results for the gmt immunogenicity endpoint for children two through four years of age are displayed here among participants in the evaluable immunogenicity population without evidence of sars kobe 2 infection the ratio of gmts was 1.3 which met the success criteria for immunobridging as the lower bound of the two-sided ninety-five percent confidence interval was greater than 0.67 and the point estimate was greater than or equal to 1.
results for subgroup analyses of the gmts in children two through four years of age by baseline stars coveted status are displayed here participants with positive baseline stars coveted status had numerically higher gmts compared to those negative at baseline which is consistent with immunogenicity results results observed in older age groups there were small numbers of baseline positive participants as there were only 13 in the vaccine group and eight in the placebo group and again this does not account for participants that became infected after dose one but before one month post dose iii results for the sierra response rate immunogenicity endpoint for children two through four years of age are displayed here among participants in the evaluable immunogenicity population without prior evidence of sars covi2 infection the percent difference in serous response rates was 1.2 which met the success criteria as the lower bound of the two-sided ninety-five percent confidence interval was greater than negative ten percent an additional exploratory immunogenicity analysis was performed and randomly selected subsets of participants from each age group without evidence of priorosar's cov2 infection neutralization of the reference strain delta and omicron variants were evaluated using a non-validated assay measured before dose 3 and 1 month after dose 3.
the neutralizing titers at 1 month post dose 3 are displayed here with the geometric fold rise from the baseline tide are also shown these results indicate that the third vaccine dose elicits neutralizing titers against all three sars kobe 2 viruses and notable is that the notes the omicron neutralizing titers are approximately six fold lower than neutralizing titers against the delta variant and reference string we'll now move on to the descriptive vaccine efficacy data this slide provides the blinded follow-up time after dose 3 for each age group in the dose 3 all-available efficacy population just over 30 percent of participants had follow-up duration of 2 months or longer the median efficacy follow-up time after dose 3 for the younger age group was 1.3 months or 5 weeks and the older age group the median follow-up time after dose 3 was 1.4 months or 6 weeks for participants 6-23 months of age the median timing of dose 3 administration after dose 2 of vaccine was 16 weeks with a range of 8 to 31.9 weeks for placebo the median was 15.9 weeks with a range of 8 to 35 weeks for participants two through four years of age the median timing of dose 3 administration after dose 2 of vaccine was 11 weeks with a range of 8 to 34.1 weeks and if placebo was 11 weeks with a range of 8 to 31.1 weeks of note the following vaccine efficacy estimates are preliminary as a total of 21 cases were not accrued and the analyses are not presented in the protocol specified efficacy analysis population in participants 6 through 23 months of age with and without evidence of sars kobe 2 infection prior to 7 days after dose 3 the observed vaccine efficacy against confirmed covid19 occurring at least seven days after dose 3 was 75.6 with a lower limit of the 95 confidence interval of negative 369.1 based on one case in the vaccine group compared to two in the placebo group again vaccine efficacy post dose 3 cannot be precisely estimated due to the limited number of cases accrued during blinded follow-up as reflected by the very wide confidence interval seen here vaccine efficacy in the dose 1 all available efficacy population for any confirmed covid19 case that occurred after dose 1 is displayed here to show the progression of vaccine efficacy following dose 1 in the top row which was approximately 14 percent the vaccine efficacy estimates varied between dose 2 and 3 and following dose 3 the preliminary vaccine estimate appears improved but again has a very wide confidence interval and a lower limit of negative three hundred and seventy point one here is a cumulative incident incidence curve for participants 6 to 23 months of age for confirmed covet 19 cases occurring at any time after dose 1.
covet 19 disease onset appears to occur similarly for both vaccine and placebo recipients until closer to the data cut off at which point the curves begin to diverge dose 2 is administered 3 weeks after dose 1 so that's easy to track on this curve near the 21 day mark on the bottom axis but there's no clear and so you don't see a clear effect of dose 2 on the incidence of cases between the treatment groups what's a little more difficult to identify is the time point for dose 3 because there are very very there are highly variable dosing intervals between doses 2 and 3 with a median interval of 112 days at a range of 56 to 245 days we'll move on to the older age group here participants 2 through four years of age with and without evidence of sars kobe 2 infection prior to dose 3. the observed vaccine efficacy against confirmed covid19 occurring at least 7 days after dose 3 was 82.4 percent with the lower bound of the 95 percent confidence interval of negative 7.6 this is based on two covet cases in the vaccine group compared to five in the placebo group the vaccine advocacy posto3 cannot be precisely estimated due to the limit due to the limited number of cases accrued during blinded follow-up as reflected by the wide confidence intervals associated with these estimates here you see the vaccine efficacy in the dose 1 all available advocacy population for any confirmed covet 19 case that occurred after dose 1.
this shows the progression of vaccine efficacy following dose 1 in the top row which was 32.6 and then the vaccine efficacy estimates between dose 2 and 3 varied and following dose 3 the preliminary vaccine estimate vaccine efficacy estimate appears approved and again with a very wide confidence intervals and a lower limit of negative eight and here is the corresponding cumulative incidence curve for participants two through four years of age for confirmed covid19 cases occurring anytime after dose one living 19 disease onset appears to occur similarly for both vaccine and placebo groups until around the midway point of the curve where they begin to diverge slowly dose 2 is administered about three weeks after dose one so you can track that on the lower axis near the 21 day mark and you don't see a clear benefit of dose 2 on the incidence of cases what's more difficult again is the time point for dose 3 because there are highly variable dosing intervals between doses 2 and 3 with a median of 77 days and a range of 42 to 239 days additional considerations about the descriptive efficacy analyses are provided here all cases occur during a time period when omicron is a predominant circulating variant there is one hospitalization for severe covid19 disease and a two-year-old vaccine recipient which occurred 99 days after dose 2.
the other 7 severe cases that occurred any time after dose 1 met severe criteria because of one vital sign measurement which was not considered clinically significant and they were not hospitalized for covet 19. interpretation of these vaccine efficacy estimates is limited by the small small number of confirmed cases and the short duration of follow-up after dose 3 which was only 35 days for the participants in the younger age group and 40 days in the participants in the older age group we will now move on to the phase 2 3 safety data this slide provides the total follow-up time combining blinded and open label follow-up after dose 3 in the safety population the blind and follow-up time durations are the same as the dose 3 efficacy populations described earlier the median total follow-up time after dose 3 for both age groups was 2.1 months approximately 60 percent of participants 6 through 23 months of age and 57 percent of participants two through four years of age had more than two months of total follow-up time here we see the analyses for immediate adverse events and there are very few immediate adverse events defined as an adverse event reported within 30 minutes of any vaccine dose the events reported were consistent with local solicited adverse events and there were no anaphylaxis events reported within 30 minutes of vaccine here you can see the frequency of local reactions in children 6 through 23 months of age including injection sites tenderness redness and swelling pain at the injection site was reported most commonly followed by redness and then swelling local reactions generally occurred at similar frequencies after any dose with slightly less frequency with subsequent doses median day of onset and duration was one to two days for all doses and treatment arms there are very few severe reactions with 0.1 percent reporting tenderness at the injection site post dose 2 and 0.3 percent reporting redness post dose 3.
here are the frequencies of local reactions in children 2 through 4 years of age my slides are jumping let me go back to that slide local reactogenicity for the older age group included injections like pain redness and swelling pain at the injection site was reported most commonly followed by redness and swelling and local reactions generally occurred at similar frequencies after each dose local reactions graded as severe were very uncommon seen in only 0.1 percent of participants for redness at injection sites followed followed by dose one and two the median day of onset and duration was one to two days for all doses and treatment arms solicited systemic reactions in vaccine recipients occurred at similar frequencies after any dose with decreasing frequency with subsequent doses the median day of onset and duration was due days for all doses and treatment arms severe systemic reactions were reported by 0.6 percent or less of participants following any dose the percentage of participants 6 through 23 months of age who reported e-diary data and who were also baseline stars cov2-positive was 7.5 subgroup analyses of solicited adverse reactions by baseline sars covey2 status showed similar reactogenicity profiles of note three vaccine recipients reported a fever greater than 40 celsius 40 degrees celsius as noted in the briefing document here is the first part of the systemic solicitor reactions for children two through four years of age of note these are different than for children than for the children the younger age group based on appropriate age appro age appropriate reporting solicited systemic adverse reactions in the vaccine recipients generally occurred at similar frequencies after any dose or with decreasing frequency with subsequent doses the median day of onset was one to two days and the median duration was also one to date one to two days for all doses and treatment arms of note vaccine recipients two through four years of age reported a fever of greater than 440 degrees celsius as noted in the briefing document as well here's the continuation of the solicit stomach reactions for participants two through four years of age solicited systemic adverse reactions in the vaccine recipients generally occurred at similar frequencies after any dose or with decreasing frequency with subsequent doses the percentages of participants who use antipyretic or pain medication within seven days of each study intervention are shown as well the percentage of participants two through four years of age who reported e diary data who were also baseline stars kobe 2 positive was 12.6 percent subgroup analyses of solicited adverse reactions in each age group by baseline stars cov2 status showed similar reactogenicity profiles the frequencies of unsolicited adverse events by age groups were shown there let me see if i can go back okay the most commonly reported adverse events were consistent with solicited adverse reactions or events which commonly occur in this age group such as infections and injuries considered not related to the study intervention the events that were considered related to vaccine included lymphadenopathy and hypersensitivity as has been previously described analyses for the adverse events of clinical interest are displayed for both age groups here the fda conducted standardized medra queries or smqs to evaluate for constellations of unsolicited adverse events no new or unexpected adverse reactions were identified based on smq results for either age group lymphadenopathy and hypersensitivity events were noted in both age groups and were previously seen in older age groups for lymphadenopathy there were three events reported from both age groups all from vaccine recipients and for hypersensitivity the incidence for hypersensitivity events was actually similar between treatment groups most were skin and subcutaneous tissue disorders commonly seen in this age group such as rash eczema atopic dermatitis and contact dermatitis there were no vaccine-related events of anaphylaxis reported here are the series adverse events or saes for each age group for the younger age group 3.1 percent of vaccine recipients and 2.3 percent of placebo recipients reported saes most for common gi or respiratory illnesses or infections that occur in this age group and none were considered related to the vaccine for the older age group 0.7 vaccine recipients and 0.9 percent of placebo recipients reported saes one participant reported two saes of fever and calf pain which were considered possibly related to the vaccine by the investigator however the fda considered the events to be potentially consistent with symptoms of viral myositis there are no notable differences found in the type frequency or severity of unsolicited aes or serious aes in either group in serial positive subjects relative to zero negative subjects and there are no deaths reported in the study now we will review the pharmacovigilance plan for the pharma for the pfizer beyond decoved 19 vaccine the sponsor submitted a pharmacovigilance plan to monitor safety concerns that could be associated with a pfizer beyond tech covid19 vaccine the sponsor identified anaphylaxis myocarditis and pericarditis as important identified risks and vaccine-associated enhanced disease as an important potential risk use in pregnancy and lactation vaccine effectiveness and use in pediatric individuals under six months of age are areas the sponsor identified as missing information the pharmacovigilance plan is for all indications as it lists youth and pregnancy and lactation which is not applicable for individuals six months to four years of age receiving the vaccine the pharmacovigilance activities under the eua include adverse event reporting which may come from vaccine recipients vaccination providers the sponsor or through the cdcv safe program reports from vaccine recipients are voluntary both the sponsor and vaccine providers administering the pfizer beyond tech covid19 vaccine must report to verse the following information serious adverse events irrespective of attribution to vaccination any cases of multi-system inflammatory syndrome cases of copin 19 that result in hospitalization or death additionally following the approval of community the sponsor was also asked to submit reports of myocarditis and pericarditis as 15-day reports to vares the sponsor will also conduct periodic aggregate review of safety data and submit periodic safety reports at monthly intervals for fda review furthermore the sponsor has planned surveillance studies that are summarized on the next slide the sponsor's pharmacovigilance activities also include post authorization surveillance studies which covers all indications for use not just this pediatric age group there are four post authorization state safety studies and one post authorization vaccine effectiveness study that include individuals six months through four years of age study c4591009 will assess the occurrence of safety events of interest including myocarditis and pericarditis and the general u.s population of all ages in the u.s sentinel system study c4591021 is being conducted in europe and will assess whether an increased risk of pre-specified adverse events of special interests including myocarditis and pericarditis exif following the administration of the pfizer beyond tech covet-19 vaccine a sub-study of this study is being conducted in europe and will describe the clinical course of myocarditis and pericarditis following administration of the pfizer beyond that covid19 vaccine study c4591036 is being conducted in collaboration with the national heart lung and blood institute's pediatric heart network and will characterize the clinical course risk factors resolution long-term sequelae and quality of life in children and young adults under 21 years of age with acute post-vaccine myocarditis and pericarditis study c4591014 is a vaccine effectiveness study being conducted at kaiser permanente southern california that will include individuals 6 months to 4 years of age and next i'll go ahead and summarize the benefits and the risks for this age group the known potential the known and potential benefits include the prevention of symptomatic covid19 based on successful immunobridging analyses to allow for inference of effectiveness for individuals six months to four years of age preliminary evidence of vaccine efficacy against covid19 and descriptive analyses and the expectation of greater effectiveness against more severe covid19 uncertainties and that the benefits include vaccine efficacy against emerging sars kobe 2 variants the long-term effects of covid19 the effectiveness in certain populations and the duration of protection the known and potential risks include reactogenicity myocarditis lymphadenopathy anaphylaxis and hypersensitivity reaction the uncertainties and risks include the stacy in certain populations and adverse events that are uncommon or that require longer follow-up to be detected and here i will end with our voting questions for our committee members today based on the totality of scientific evidence available see the benefits of the pfizer beyond tech covid19 vaccine when administered as a three dose series three micrograms each dose outweigh its risks for use in infants and children six months through four years of age thanks so much thank you dr wallace shine very succinct and careful presentation dr cohen you've got your hand raised followed by dr bernstein thanks dr wellesheim that was uh really an incredible presentation um i really appreciate the transparency and clarity um two questions one is is it possible um for fda or did you tease out reactogenicity in the population of um individ of infants and young children who got vaccinated with that third dose between eight and 12 weeks and is it similar to the kids who got vaccinated uh more towards the median third dose interval that was done in the study and then my second question is when you um is the fda assessment that the three dose primary series of pfizer is equivalent is based on immunogenic immunobridging studies uh meets the criteria compared to two doses of um of adult vaccine or are you able to also feel confident that it would be similar to three doses in the adult vaccine thanks dr cohen for great questions as always your first question was related to reactogenicity based on the dose interval between dose 2 and dose 3 if i understand the question and we did try to do that analysis and from what i recall from that i'm sorry i don't have a slide to show you with those numbers there was no significant difference in the reactorgenicity based on dose interval and your second question i think is related to comparisons of vaccine effectiveness following two doses in adults or three doses of adults is that correct yes okay thank you and i think that's that's a difficult question to address based on the data that we have here because our immunogenicity comparisons are to adults who receive the two dose primary series um there's further discussion in some of the benefit risk profile and within our briefing document with the benefit of the third dose for adults and so i think that that benefit is really reflected by the variant that's circulating currently the omicron variant and i don't know that the data would be available from the appropriate time periods to make that comparison at this point if that makes sense because we don't have data pre-omicron for these younger age groups so would you is fda's assessment though that there would also need to be an additional dose a booster dose in this population that's a great question thank you um and i might defer to dr fink if he wants to um weigh in here because it's a bit beyond the scope of the data that i presented from the study here thank you yes thanks susan happy to weigh in i i think we we have a situation here where as you've seen from the the pfizer presentation and fda's independent analysis of the data we have some very preliminary vaccine efficacy results after dose 3 that are limited by a small number of cases and limited follow-up time that appear to suggest a improvement in protection following dose 3 following as compared to following dose 2.
we do consider this estimate to be preliminary we consider it to be imprecise and potentially unstable and so exactly what the vaccine efficacy is after dose 3 i think needs further data to inform uh and uh we would expect to uh you know get some of these data uh hopefully from uh updated analyses from the the clinical trial if more cases are accrued recognizing of course that if the vaccine is authorized um that will result in unblinding of placebo recipients so that they can get their uh through their series and also from real world uh effectiveness data uh once the backseat is is used um i do want to make it very clear that that based on the totality of evidence that that we've presented uh including primarily the amino immunobridging data to the two dose adult primary series as well as a number of pieces of supportive data including preliminary descriptive efficacy analyses and other inferential lines of data that you've seen from from pfizer that we do feel very confident that the uh that the evidentiary standard for for benefit for eua has been met here but i think uh you know in terms of what the efficacy is after a third dose and whether an additional dose beyond that would be needed is going to require a little bit more data to sort out thank you dr pink uh we're moving on two more questions uh we have a hard stop or one more question from dr office we uh dr bernstein you're next thanks um i'm juggling things here uh great presentation dr wala shine and i just had a question could you go to slide 27 please with the omicron neutralization analysis that was done they uh they used the fluorescent focus reduction neutralization test and on slide 27 it shows i think it's a 5d pointer yeah on that slide it shows that the post those three gmts against omicron were lower as compared to the ancestral strain and the delta variant what's the clinical significance of that thank you for the question and i think that that is a great question because we're not sure we don't have a correlative protection additionally this is a non-validated assay that's been used just to have this information so that we can see that there is neutralization of these various viruses the clinical interpretation though i think is limited at this point um in terms of what i my understanding of what this assay shows i welcome dr fink um if he has additional insights to interpretation of these numbers as well thank you i think what we can say is that the data you see on the slide here tracks with what we've seen in real world effectiveness studies and immunogenicity studies of this vaccine and other vaccine in older age groups that the neutralizing antibody titers are lower for omicron compared to delta and the ancestral strain and that that does correlate with a lower uh level of effectiveness against at least more mild disease and in some cases more severe disease due to omicron than uh than the delta variant and ancestral strain i'm trying to get our our organizers the time to prepare for the for the oph uh doctor off it please okay so doctor wallace again thank you for that clear presentation what i'm trying to understand if you look back in december 2020 when we considered the fives from modern vaccines as two dose vaccines they were essentially equivalent in terms of advocacy similarly if you look at the efficacy for two doses of fisa versus modernity for the 12 to 17 year old or the the six to 11 year old again they tracked as being similar this is the first time you're really seeing a difference in the less than five-year-old where two doses of modern it does offer some level of protection whereas that wasn't true at all for the defies of vaccine and the challenge strength were essentially identical which is the um era and i realized these weren't side to side comparisons but you have any sense of why that would be true why there was for the first time a clear difference where pfizers didn't present didn't protect after two doses where the derna had where they had tractors similarly previously thanks dr effett great question of course and it's i don't i don't want to say impossible but it's difficult really to make the comparisons between these two vaccines so i would you know i don't think we could really move there with the data that we have but thank you for the question and we can revisit that question later on because i'm sure it's going to come up again thank you to all our presenters it's now time for a half hour break we will resume at 1 p.m uh eastern for the oral present oral public hearings the oph all right thank you arnold and yes let's take us to break please hold off members for a moment before we go to break studio please uh put this on break [Music] so [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Applause] [Music] so [Music] foreign [Music] [Music] um [Music] uh [Music] so [Music] [Music] so [Music] [Music] [Music] [Music] [Music] [Music] so [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] um [Music] [Music] [Music] [Music] [Music] so [Music] [Music] do [Music] [Music] [Music] so [Music] do [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] good afternoon and welcome back from that our lunch break to the 174th vaccines and related biological products advisory committee meeting day two i'd now like to hand this meeting over to our chair uh dr monto and uh as well as peter marks uh take it away arnold i'd like to welcome you back and to the open public hearing session please note that both the food and drug administration and the public believe in the transparent process for information gathering and decision-making to ensure such transparency at the open public hearing session of the advisory committee meeting fda believes that it is important to understand the context of an individual's presentation for this reason fda encourages you the open public hearing speaker at the beginning of your written or oral statement to advise the committee of any financial relationship that you may have with a sponsor its product and if known it's direct competitors for example this financial information may include the sponsor's payment of expenses in connection with your presentation in this meeting likewise fda encourages you at the beginning of your statement to advise the committee if you do not have any financial relationships if you choose not to address this issue of financial relationships at the beginning of your statement it will not preclude you from speaking dr marx please thanks very much dr monto and thank you to the open public hearing speakers as noted fba welcomes comments from interested members of the public during the open public hearing portion of the advisory committee meeting we welcome and respect the input about the topics being discussed at today's meeting but we don't in any way accept or condone comments that include incentive remarks or hate speech particularly any such remarks directed at a member of the advisory committee or fda staff thanks very much thank you um this is prabhupada before i begin calling the registered speakers i would like to add the following additional guidance fda encourages participation from all public stakeholders in the decision making processes our evil advisory committee meeting includes an open public hearing session during which interested persons may present information or views participants during the oph sessions are not fda employees are members of this advisory committee fda recognizes that the speakers may represent a range of viewpoints these statements made during this open public hearing session reflect the viewpoints of the individual speakers or their organizations and are not meant to indicate agency agreement with the statement made with this additional guidance i would like to now call upon the first speaker dr jasmine king you have three minutes to speak hello i'd ask my first and only slide be presented my name is jasmine king my health and life have been completely altered since july of 2021 when i received a single modern vaccination i was 38 at the time it does take an awful lot of courage to open up to a group of strangers about such personal matters then again the life-threatening health issues i am facing have evolved a level of courage and bravery i could never before have fathomed before this vaccination i was active energetic upbeat and my husband and i run an organic farm i as the grant writer attorney i ran taught yoga i recently very recently had two natural births and was breastfeeding my one-year-old at this time i ignored the initial hit the vaccine took on me regarding this as quote to be expected but the compromise on my immune system started showing within days i had previously been able to avoid the dozens of annual colds my two travelers get but after vaccination i quickly caught their cold it happened again and again then a topical fungal infection and a few weeks in i began experiencing subtle muscle spasms and sensory issues i constantly felt unusually hot burnt on my skin or as if something invisible was crawling on me how odd i thought i had no idea my nervous system which culminated explosively two months later my back arm has burned it scorched by fire the pain went deep into my muscles zaps and blooms were sounding in my head my clients all swelled up my sweating became abnormal making me intolerant to heat and my heart rate doubled electric pins and needles twitches and muscle spasms that were strong enough to jolt me in my sleep passed over every body part for weeks and it was also aggressive that i could not sleep for six weeks then in late december i um notable muscle wasting or atrophy began and it began in a painful manner um while i'm told that modernist trials resulted in absolutely zero neurological adverse effects there are thousands of individuals like myself i found this out after testing positive eventually that is for an antibody related to sensory and neuromuscular issues i initially joined a male patient support form then found other similar forms where the exacting injured individuals are congregating for pure assistance i also learned this upon trying to get into several prominent neurological or neurology clinics and they're all backed up many of those injured experienced these side effects long before i was vaccinated yet i wasn't afforded this knowledge no disclosures no psas from federal health agencies and no media coverage process whatsoever apparent from where i stand is a missed opportunity to collect and act on neurological vaccination risks in the non-trial population to inform the public and disseminate the trends and medical providers particularly neurologists this lack of dissemination hurts my ability to be quickly treated and i'd like everyone to understand that it affects at the patient level now i also see from where i now am that it is slightly odd and flawed to rely so extensively on self-reporting when persons like myself are going through crises that compares to nothing i've ever been through my entire life but it is even more flawed to sit on this data of the non-trial population for years to later do a look back i believe this is the approach right now that explains why there's so little discussion of this i understand from a statistical standpoint but given what is at stake i do not understand me can you please wrap it up i need that absolutely yes as you contemplate the decisions ahead please keep in mind that there are mandates and immense pressures involved here i believe there's more room for paralyzed comparisons for example looking at my age group and health profile i had minimum risk in the virus itself how does this apply to young children likewise just because of vaccinations i'm sorry that there's a lot of looking at the hospitalization rates of virus versus vaccine but you take a case like mine i haven't been trying to you have to end it here please okay well thank you all okay so the next speaker is dr ashley serrano you have three minutes hi i have no conflicts my name is ashley and i am a mother of a three-year-old as well as a clinical psychologist who focuses my work on evaluating and treating youth i am here again today to strongly urge the community to recommend emergency use authorization for both the pfizers and madrid vaccines in children under five years as i mentioned yesterday i was when i was referring to children under five madonna easily met immunobridging endpoints after just two doses for the five and a younger age group this will give our children full protection more quickly when compared to pfizer's vaccine which means they would start the school year fully vaccinated that's really great news for my daughter four children six months to five years of age modernist trudeau series also showed improved efficacy when comparing it to pfizer's data against omicron after two doses we know both these vaccines would eventually require what we now call booster doses and applying the third dose from aderna and perhaps a force for pfizer next slide piece it took me a long while to conceive my daughter but it wasn't without the help of amazing scientists within the infertility world to help me these are just a few of the supplies i used throughout the many months of infertility treatment many other of these supplies would have been in various airports and hotels that we are a family who love to travel this is also me the night before i was rushed to the hospital via ambulance and little did i know that i would be meeting my daughter just a couple of days later who could have known that after my daughter's first christmas would be her last time visiting most of her family members for over two years she was just an infant the last time she saw them in person or at all you should see her face when she gets to see our family members via video and i can only imagine what it will be like when she gets to see them in person once she is fully vaccinated slide four please when i had my daughter i had so many dreams for her and couldn't wait to share all of the experiences with her it was already sad that we didn't have toys r us but once march 2020 came we lost so many other opportunities to visit family in other countries and states swim lessons birthday parties and the list goes on i never would have thought i'd have to take more than normal precautions at a lake or playground to protect us from potentially fatal illnesses it has always been my goal to protect her ranging from proper prenatal care to wearing sunscreen to receiving all the vaccines to protect against potentially fatal diseases as a three-year-old she is now asking to go inside stores restaurants and people's houses all things that were completely normal for us at three years old but i often have to say no because my job is to protect her all she wants to do when she is vaccinated is to go into a restaurant and have an indoor elsa birthday party as a clinical psychologist i evaluate zero to five-year-olds for autism when colvin 19 came i collaborated with colleagues to create a virtual evaluation to allow these children to obtain appropriate treatment we continue offering these virtual evaluations because this age can't be vaccinated yet many families don't feel comfortable taking their unvaccinated children to playgrounds to strengthen their skills we continue offering telehealth but what happens when telehealth is no longer covered by insurance or when the public health emergency expires next month now is the time to approve these faculties for this age group finally while many people resume life as normal there are many kids and teenagers who have not my family has not since my three-year-old continues to be ineligible for the vaccine 399 days since our teenagers became eligible to be vaccinated let's help our future generations start living now and allow them to be protected against the harms of carbon 19.
Thank you thank you the next speaker is mr michael baker good afternoon members of the committee thank you for listening to my statement i have no financial conflicts of interest i'm a father of two wonderful children ages one and three and i would like to take a moment to talk about how the past two years have impacted our lives this slide is a non-exhaustive list of some of the things that we have missed out on and although what i've shared here is specific to my family our experiences are in no way unique our children have all to one degree or another than subject to the largest social experiment in history and it will be many years before we fully understand the developmental impact that this pandemic has caused my wife and i have had to continuously weigh the risk of disease against the risk of stunted development for our children and every single day i fear for them i want to make the best choices for my children as i possibly can and i ask myself constantly have we made the right choice and yet for all that burden i am endlessly grateful we have been incredibly privileged to have had the option to make these choices not all parents in our position have had the choice to do what they thought was best this problem has only become worse pediatric infections have skyrocketed as the rest of the country has in many ways completely moved on all i am asking is now that the rest of the country can choose not to care about covid that i have the choice to vaccinate my children and i have the choice to do it in the most timely fashion possible we have utterly failed as a society to protect those among us who cannot protect themselves there have been as you know nearly 1600 pediatric deaths due to covet 19 as of june 12th thousands more hospitalizations and an unknown number of future potential complications as we can no longer rely on any sort of layered mitigation to control the spread vaccination is our last remaining hope it must be offered as an option with all due haste and this committee should consider the differences between each vaccine through a lens of equity there is a vast difference for working families between making it to two appointments versus three and there is a vast difference in waiting an additional seven weeks to be fully vaccinated i have been listening to today's meeting and i want to reiterate that i understand a booster dose will likely be needed at some point my primary concern as a parent is not to avoid symptomatic illness it is to keep my children out of the hospital and safe from serious harm my wife and i have succeeded in keeping kovit out of our household thus far but now we are calling on you to help us take one small step back into normalcy we are asking for options for us the superior option will be vaccination with moderna for others it may be pfizer we ask that you afford us and all parents who wish to protect their children the possibility to make that choice now thank you for your time thank you for allowing me to speak today i have no conflicts my name is fatima khan and i am a mother to a six and four-year-old i am also a co-founder protect your future and entirely volunteer grassroots group of physicians parents and activists advocating for health leaders to prioritize children including allowing our youngest equitable access to safe code vaccines we receive no funding from any individual or corporation our group is composed of thousands of families who accept that covid can pose significant harm to children and that vaccines offer a strong layer of protection against not only infection but also long-term complications like misc long-covet neurological effects and in worst cases death based on all available data we support emergency youth authorization for both moderna and pfizer's coveted vaccines our public health leaders have left families of children under five behind making any semblance of a balanced life difficult to achieve as a co-founder of protect their future i hear from families across the country struggling to keep their children safe while also balancing real life necessities such as work school and other obligations not a day goes by that i don't hear of a parent lamenting that their child either contracted covid or was exposed despite taking all reasonable precautions each parent feels an overwhelming sense of failure and defeat because they weren't able to keep their child protected until a vaccine was available for their age group we know that families of color and low-income families have greatly suffered these are often the families who don't have the choice to keep their children home and who must make impossible decisions between protecting their loved ones and bringing food to their tables delaying vaccines to our youngest only exacerbates these disparities almost eight months out from when children five and older could access vaccines millions of children under five have been infected moreover the majority of hospitalizations and deaths recorded in children under five occurred during the omicon surge a time when trials were meant to have already been completed in this age group any more death and illness for our youngest and most vulnerable is unacceptable every day of inaction leads to more suffering and damage as others stated yesterday moderna was shown to not only meet trial criteria for the two dose regimen but also had a higher efficacy rate against omicron when compared to pfizer's two-dose series it seems to be the case that pfizer's efficacy improves significantly after a third dose and it can be inferred that a third dose of moderna like boosters for other age groups will yield even better results than the two dose regimen moderna also showed higher antibody levels after just two doses than pfizer's three dose series trial and real world data have are approving moderna may be offering superior protection this is why it is critical to approve both vaccines today so that parents have options and so that our children can be fully vaccinated before school if they need additional doses later that can be evaluated as needed children like my daughter who will proudly join the ranks of junior kindergarten this fall must have access the same access the rest of their school-aged peers has we have waited too long and too many families have suffered already please ensure that our children are protected with these highly safe and effective vaccines thank you thank you the next speaker is uh mr nicholas giglia thank you for the opportunity to speak i have no conflicts i am nicholas julia father of two great kids a supernaturally empathetic son and an energetic and curious daughter who participated in the pfizer trial i'm so grateful we could contribute in a small way to this wonderful scientific achievement and i look forward to one day telling my little girl how she helped save the world it is vital to approve both these vaccines the three dose regiment from pfizer and the two dose regiment from the durna have both met immunobridging the primary goal of the study without any major safety concerns modernist two-dose regimen would allow kids like my son to start preschool with kindergarten fully vaccinated and the pfizer vaccine provides protection spread out over three doses parents and children deserve a choice especially since our only choice up to now has been hope and prayer we have through a combination of precautions remote work and luck kept coveted based so far this has come at a high price of my mental health my waistline sleepless nights deferred dreams and the childhood i wish i could have given my kids every decision requires detailed and exhausting risk calculation and i wonder at every day care drop-off that today is the day our luck runs out when exposed the kids are home for seven to ten days where we have to be full-time employees and full-time parents while feeling like we're failing at both we have navigated a world without protection or empathy while those of the luxuries have moved on through coven we've heard constantly that we have the tools to end the pandemic while we were prohibited from using these tools to protect our children we must grant children under five access to these two safe and effective vaccines especially during a search these applications are welcome but this meeting should not be considered victory our governments have abandoned the youngest children allowing millions to be infected with a novel virus with unknown long-term effects without the protection vaccines offer process is important and necessary but the circuitous route we've taken to get here including unexplained trial expansions cancelled meetings deferred applications and almost a year of promises of release in the coming weeks has robbed this day of the joy i expected to feel real families have been impacted by every twisted turn in this process in my line of work it is vital to take an honest look at issues to prevent recurrence and it must happen here as well we must proceed from approval to detailed transparent after-action reviews to understand how to streamline the approval process for the omicron specific booster that i'm sure is coming and unfortunately the next pandemic without sacrificing the rigor i saw firsthand in the pfizer trial there has been much sacrifice to get here from health workers trial families the hundreds of children who have died from covet and the countless children and families that may never be the same we must honor these sacrifices by approving both applications while acknowledging we can never leave our children behind again thank you thank you the next speaker is lauren dunnington you have three minutes good afternoon my name is lauren dunnington i work in global public health and i'm the parent of two children under five in washington state i have no conflict my comment today is broadly in support of emergency use authorization for both the moderna and pfizer vaccines for children under five just last week my kids had yet another cova 19 exposure at daycare the toddler came home with a fever and i felt my stomach not up we had coveted in december and i kept asking what's the impact going to be of a repeat coveted infection in my unvaccinated child in may my friend's four-year-old was hospitalized due to covid19 i asked that parent what she'd like me to say to the fda on her path her response was my daughter was not yet eligible for a vaccine and public health protections like masking had ended a vaccine could have offered my daughter protection and prevented a four night hospital stay i remain concerned about coven 19 and its sequela and i want more tools in my toolbox to protect my kids especially my toddler who cannot mask safely we've seen increased incidence of diabetes multi-system inflammatory syndrome myocarditis brain fog and even potentially hepatitis in kids with a history of cova-19 infection we know that these mrna vaccines are safe and effective nine million kids over five have received an mrna covered vaccine in the united states and in germany tens of thousands of under fives have been safely vaccinated off off-label it's been a long anxious and frustrating wait especially knowing now that the fda has had moderna data to review since april i cannot know the fda's inner workings but i can say that the lack of transparency as to why the moderna under five review has taken longer than any other age cohort has made me feel like vaccinating my kids was not a priority for the fda but i'm grateful that we're finally here and i have some important requests about how we move forward first please approve both vaccines the data shows that we have two effective options for our kids and families deserve a choice based on their circumstances we know that boosters and a moderna third dose are likely to come in the future but as the parent of a child starting kindergarten at the end of summer i would like the option of the six-week modernist series that shows superior immunobridging after two doses to give my child the best protection as she begins the school year this shorter series also reduces the burden on families who use public transit or have to take time off work to get kids vaccinated the 13 week visor series will leave incoming kindergartners with less protection when school starts i also want to emphasize access i'd like to see emergency authorization for pharmacists to be able to vaccinate children under age three enabling pharmacies to vaccinate our youngest would produce the bottlenecks at pediatric clinics where providers will now have to accommodate vaccination on top of a regular patient workload and finally i want to mention boosters looking ahead our youngest kids must get on the same track as adults with access access to updated boosters that protect against new coping 19 variants delays with eua vaccine access and boosters have real life consequences for our families every single day matters for our kids thank you and please approve these vaccines for under five thank you the next speaker is uh stepping off mentally i have no conflicts hello everyone i'm kathleen hunsley with friends of the constitution today i'll be presenting some facts for your consideration but i want you to know that i fully understand how hard it is for you to be in your position and being literally inundated with facts everyone wants to do the right thing but what is the right thing that's a question that can be mind-boggling at best i'm hoping that what i say today will relieve some of the stress and fill you with a clear and peaceful understanding of the truth and now for the promised facts the fda is legally prohibited from approving any biological product for emergency use unless all of the following conditions are met there must be an emergency that poses a risk of death to the target group the product must be effective in preventing the disease it must be safe and finally the benefits must outweigh the risk with regard to the first point children without comorbidities who acquire code 19 have a 99.98 survival rate there is no emergency moving forward to effectiveness a study by kyle a biddy which includes the data analysis of 145 countries found that covet 19 vaccines were in fact associated with a 38 increase in covic cases and a 31 increase in deaths could these vaccines be negatively affecting immunity the number of severe efforts events affecting children ages 5 to 17 reported to bars as of june 3rd with 8 811 including 114 best and 1 346 cases of myocarditis a condition that can be fatal we can assume that if these vaccines are authorized some babies will die the benefits of these vaccines are questionable and the risks are clear think about your personal priorities your concerns for your reputation your job the approval of family and friends and issues concerning the financial security of you and your loved ones as well as your private thoughts about some of the information you have reviewed these concerns do matter but there is something that matters more if these vaccines are authorized some babies will die if you were alone and saw a baby of six months old right in front of you would you yourself take a load of firearm and kill that child my guess is the answer would be no and yet if you participate in authorizing these dangerous injections for this age group you in fact will be doing that how would you feel about that at the end of your life when none of the other things matter how would your soul feel that's all you need to ask yourself in making the right decision thank you very much thank you the next speaker is melissa bremen you have three minutes my name is melissa braisman i'm a pediatrician and a mother i have no conflicts i implore you to recommend eua of the modern vaccine presented today personal freedom arguments have led to removal of nearly all mitigation effectively forcing parents to choose between safeguarding their children and participating in society under twos can't mask two to fours don't mask well we must provide parents the choice to vaccinate their children when benefits still clearly exceed risks moderato's vaccine offers similar efficacy against symptomatic omicron and young children as is afforded to adults and this is so much better than nothing we can expect modernist booster will further improve protection in young children and i'm thrilled these studies are underway crucially modernist current mrna vaccine continues to offer robust protection against severe omicron disease and adults and we have every reason to expect the same will hold true for young children and it will provide proven protection before the new school year begins this vaccine is also incredibly safe at efd's usual rigorous standards which is fantastic thank goodness we are finally here but this day is bittersweet the fda must adapt its approach so that young children's access to updated vaccines and therapeutics doesn't continually lag 18 months behind adults it's for this very purpose of strengthening the nation's public health protection during a public health emergency that eua exists yet there was no appearance of urgency with respect to our youngest the long wait endured due both the conventional pediatric trial designs and to unanticipated delays have been measured by families not in units of time but rather by extended isolation and excruciating sacrifice and tragically by vaccine preventable disease and disability and in some cases death it has been incredibly offensive to hear this weight trivialized as children died evidence-based medicine as i know it entails making the best possible decisions based on the available information not being absolved with the responsibility to take any action at all while deleting a perfect body of evidence that requires years to accumulate as lives hang in the balance in this speech i ask first why were age de-escalation conventions introduced so strictly during a pandemic second when will the fda revisit the exaggerated concerns about fever and febrile seizure that have impeded vaccine progress and resulted in physical vaccine being underdosed the pathophysiology that is the science doesn't support fever phobia third why was the review of modernist data delayed these decisions had profound implications for parents and children who are still waiting suspended in time 18 months after the members of this committee became vaccine eligible in sum how will the fda evolve so that children's lives are spared who among you will champion this change i am pleading with the fda to prioritize actual children's lives over an unattainable unimpeachable abstraction of perfect medicine please approve modernist lifesaving vaccine and please don't put children in this position again the fda must adapt if it hopes to maintain the trust and respect of pro-science parents we simply cannot let any more children die or suffer unnecessarily and still hold our heads high as physicians or as a nation thank you the next speaker is congressman louis gomez yes thank you very much there are many unanswered questions regarding the safety and efficacy of covid vaccines especially for babies and young children i'm deeply concerned that the push to vaccinate these children is nothing more than a dystopian experiment with unknown consequences some of us have outlined these questions in a letter to verpack but have not received any answers and i'll post some of them here the letters at my website gomer.house.gov and my twitter account at rep louis gomer but number one why has fda refused to release the hundreds of thousands of pages of data from pre-approval manufacturer studies post-approval adverse events data and other post-approval manufacturer data number two what is the cardiac risk factor in administering these covered vaccines to children number three would renowned immuno world-renowned immunologists have raised concerns about potential antibody dependent enhancement ade resulting from covert vaccines and since ade was a problem in prior unrelated respiratory vaccine trials we need to know what stead studies if any the fda has that it's used regarding potential ade from coveted vaccines in children five and under or any age group can the fda affirm that there's no risk of ade for vaccinated children number four if approved and widely used among children five and under how many lives if any does fda estimate will be saved next year given the injuries reported in the fda's vayer system how will fda evaluates serious vaccine injuries versus serious covis outcomes number five is it possible that the proposed covered vaccines in young children would create increased risk from future novel coping variants number six why has the fda recently lowered the efficacy bar for covered vaccines for youngest children this change significantly lowers the expected benefits from any covert vaccination for young children and it's of particular concern given that over 70 percent of that age cohort are already serial positive these questions and others are critical and deserve thorough answers by fda invertpack prior to any emergency use authorization with the accompanying protection from liability for all harm done in conclusion some of us have grave concerns that in balancing the risks to rewards here all the risks are to the innocent children and all the billions of dollars of rewards go to the government protected pharmaceuticals leaving me to wonder if republicans get a majority um they need to have a bill i'm working on it now to allow civil and criminal liability to vaccine providers and accessories despite an eua which should force more sensitivity to vaccine harm to our young children we've got to care more about the children and i appreciate the time to express this thank you the next speaker is the doctor klein you have three minutes thank you for allowing me to speak i'm hesitant i have no conflicts it is ready of june 10th rfk said and you have all the details so i'll just mention the main points there is no covert emergency for children that's number one number two the vaccines do not prevent transmission they do not prevent infection number six the fisa clinical trial for children two through four years old failed to meet the fda's specified requirements for covered vaccine euas they're proposing to use a product on a schedule that failed fda's established criteria in its clinical trials on page 117 of modernist submission submission they hid their clinical data and instead used the computer model as simulation when they adjusted the parameters to give them the results they wanted then on page 118 they say the risk of myocarditis was assessed using a seven day risk window a seven day risk window get the spike tax injection how's that for long-term study private claims that they did a study of 4522 participants six months to four years old this of course is a lie mike modern advisor found ways to whittle down the numbers of participants to force the data to fit a predetermined fictional narrative prizer has a unique problem and this may be one reason why it has taken us so long to get to the application stage after finders thought that this clinical trial and kiss was going to work so they unblinded it on december 20 september 28 2021 and they started vaccinating the placebo group to destroy the control and eliminate any long-term safety data on november 3rd 2021 and in early december the data showed that the trial had failed so far they had to scramble to enroll even more kids in the attempt to save the clinical trial with a certain dose the result then becomes a complete model because pfizer has to refer to the blinded period before september 28th the unblinded crossover period after september 28th and then the post-protocol amendment sixth period forever wanted data cut off of april 29th i pray that you realize that if you choose to ignore the obvious that madonna and pfizer are lying they'll be doing a great disservice to humanity you know that and it takes all if you know that all it takes is for evil to win is for good people to say nothing if you remain silent and do not call them on their lives you're allowing madonna insiders to lie to the american public and at what cost to human lives in the parent story the evil human wanted to kill all the jews mordechai said to queen esther do not think you'll be able to escape in the king's palace any more than the rest of the jews or if you persist in keeping sounds at a time like this relief and deliverance will come to the jews from some other place and you and your father's house will perish and who knows if it was for just such a time as this that you attained the royal position we are at a cosmic turning point in the history of the world we are in a war between good and evil and who knows if it was for just such a time as this that you attend your positions on the vrbtac you have a once in a lifetime opportunity to do the right thing for humanity and for god and all and you will be remembered in the history books for eternity i pray for you that you look in your hearts and souls and find the courage to stand up to the big farmer like esther stood up the humming and saved all the jews you have the opportunity to save humanity and the world has not met requirement since you're not approved you know that stand up against them on the side of god on the side of good and may god smile on you always the next speaker is kelly solar you have three minutes hello um my name is dr keeley solar i'm a phd chemist and i have no complex at all today thank you so much for the opportunity to speak today and i am a phd chemist but even more importantly i'm a mom of an under two-year-old i spoke emotionally yesterday on all the reasons why parents are desperate to vaccinate their children under five today i'm here to speak very scientifically and logically to ask you to make the only logical decision available which is to approve both the pfizer and madonna vaccines for this youngest age group based on three points number one these vaccines first and foremost have been proven to be safe number two these vaccines are effective and number three authorizing these vaccines gives all parents the ability to make the choice that they deem best for their family regarding points one and two these vaccines are safe and effective for all other age groups when the vaccines have been proven to be safe and effective we have approved after careful scientific review and without hesitation we have authorized the vaccine i would like to thank the sponsors as well as the fda cdc and the ad hoc members for all of their dedication to a rigorous and complete scientific review and presentation of the data it is very clear from the data that these vaccines are safe and the benefit of vaccination helps decrease the risks associated with covenant infection beyond prevention of symptomatic infection in addition there is additional benefit of the cellular responses which help prepare the immune system and the body to fight off future infection this is harder to measure but can be logically and scientifically inferred by the multitude of data that we have from older age cohorts and our knowledge of how vaccination and immunity work in general regarding point three and allowing parents a choice authorizing these vaccines gives all parents access to either choice that they desire to make for their children for parents without access to the choice that we desire which would be to vaccinate our children we are desperate for this choice the pandemic has moved into a personal risk benefit analysis stage where we are encouraging individuals to self-assess their risk and make decisions about their own health parents who assess that the risk benefit of these vaccines versus covenant infections have two choices to consider as it is clear that covert infection will likely become inevitable number one their cho their child could get covered without having been vaccinated or number two their child could get covered with having been vaccinated however only one of these options today is available to parents under five however my choice from these two options would be number two to vaccinate my child which is not available to me today however today we have the logical option which is based on the scientific evidence that has been amassed indicating that both of these vaccines are safe and effective and we need to allow access to both of these risk-based decision options for parents and authorize both of these vaccines i will vaccinate my daughter as soon as possible i don't want a vaccine mandate i don't want to force other parents to do the same but i want the choice and i'm asking for that choice that i desire to make for parents who choose option one decisions made today on authorization would not have to change that choice but for me and many others the decision without the authorization of these vaccines would be absolutely life-changing i urge you to make the most logical and fact-faced decision today allow us this decision to vaccinate our children and empower us as parents to protect our children thank you so much for your time today and thank you so much for your dedication to the scientific process thank you the next speaker is ashley lin you have three minutes good afternoon i'm shay and i have no financial involvement in this discussion i am a mother former educator director and recently worked as a tech manager developing startups in the health space i was never exposed to cobit 19.
My children have also been enrolled in private schools with zero exposures please recall these products immediately do not harm our low-risk children they do not need myocarditis from long-haul vaccine adverse reactions we demand informed consent as a parent i wanted to do the right thing to protect my children against covid19 so i received the first dose of pfizer on april 3rd little did i know this would be the worst day of my life after an hour i called 9-1-1 due to an anaphylactic reaction i never experienced anything like this in my entire life my heart was racing i felt so weak disoriented and vertigo almost like i was going to faint i had severe chest pains i couldn't breathe due to throat closure closure sensations i found a feverish but i was crying just an hour ago my family was present but they didn't know what to do that we just wanted to do the right thing we were informed the vaccine would be safe as our entire family and friends were all vaccinated but i felt completely betrayed and lied to i had no other choice but to call 9-1-1 for help after my fights are vaccines i was asked to stay on the phone until paramedics arrived to make sure i did nothing i honestly thought i was dying and i wasn't sure if i was having a heart attack i've always been incredibly healthy and in excellent shape i felt like my entire life left before my eyes my vision was very blurry and i couldn't stop shaking i'm still shaking right now 14 months later the paramedics finally arrived and advised me to take benadryl and i should be admitted into the er right away they assured me they would not let me die but i realized they didn't know about adverse reactions it seemed like no one was really prepared to deal with allergic reactions it almost seemed like a drug overdose i wouldn't really know since i never take medication nor do i drink alcohol at the er i was only monitored and prescribed an epipen then discharged immediately the doctor didn't feel the need to do any further testing so i received no explanation other than i had an allergic reaction i left feeling confused and i still didn't feel well and now i had to prepare to deal with allergic reactions when i never had any serious any severe allergies prior i only had a minor rash as a child due to amoxicillin prior to leaving the er i remember the er doctor being slightly confused and clearly stated only elderly people die from these issues i was surprised he would even admit to that considering my elderly relatives were just vaccinated i felt so long so lost so confused with no answers i felt dizzy my vision was affected i had to take benadryl and tylenol for a week straight they wouldn't prescribe anything else for me they didn't think this was going to be long term i i contacted my doctor almost daily my heart felt weird i felt like flutters i called i wrote emails for answers to my doctor no one knew anything i felt like i was being completely ignored and my symptoms were dismissed my doctor denied referrals to cardiology neurology and denied me of an mri i kept calling and hoping to get new doctors on call for answers through urgent care and zoom visits one doctor eventually prescribed me blood pressure medication for palpitations it was propanol did she realize i'm breastfeeding i had the worst nightmares and bringing in my ears i couldn't sleep i was afraid i would never wake up again you're a tiny duck please can you wrap it up my doctor advised me to purchase blood pressure monitor and track my blood pressure daily it was really high i never experienced this issue prior i also had internal tremors very similar to parkinson's my legs were weak and felt numb i kept thinking i'm too young to develop parkinson's or become paralyzed after two weeks of being on the heart monitor i quit taking my medication as side effects stated it may cause heart failure i was still breastfeeding and i'm worried that my child will experience long-term issues from these vaccines and adverse reactions and affect his development he's now under evaluation and may we have to move on i apologize all right next speaker next please keep catching have 3 minutes good afternoon thank you for allowing me the opportunity to speak today my name is kate shank i have no conflicts i am the mother of three children ages four years two years and seven months since the being the pandemic my husband and i have done everything we can to protect our children from coping 19.
our children haven't been inside grocery stores or department stores let alone typical childhood staples like indoor amusement parks museums malls and restaurants i am thankful that my children have remained healthy but it's been a long few years last year i was pregnant with my third child who was due in november 2021 after my husband and i received our colby vaccines as soon as they were available to us it seemed helpful that a pediatric vaccine would likely be coming in the fall around the time the new baby was due i imagine we would still have to be careful for the baby's first six months until he was old enough to be vaccinated himself but at least the risk would be somewhat mitigated since everyone else in the family would be vaccinated as we all know that pediatric vaccine didn't come last fall or in february or in april that baby is now seven months old and still none of my children are able to be vaccinated my oldest child would be five years old in mid-august she is supposed to start kindergarten on september first because of the pandemic she has stayed home with me instead of attending preschool she is so very excited for kitchen she is eager to learn and play with kids her own age because of her late birthday the only way she'll be fully vaccinated before kindergarten starts is if the under five vaccine is approved now particularly modern essence it's a shorter series magenta would allow children starting preschool and kindergarten this fall to reach the same protection antibio level in only two doses compared to pfizer's three ghost series which instead produces similar efficacy and immunobirding over a period of three months boosters could each could be each boosters for each given has been considered in the future making madonna three doses and eventually five or four i urge you to please act now to authorize emergency use of both moderna and pfizer vaccines for children under age five at this point in the pandemic many people have seemingly moved on and are completely foregoing culver precautions such as masking and social distancing and our youngest children have been left behind unprotected those without children do not even recognize the toll this has taken on young families since we have become invisible while they are living life as normal please allow parents to give their children the layer of protection that vaccination allows the data indicates that these vaccines are safe and have met immunobreaking they can protect against the most severe outcomes the things that have kept parents awake at night since being a pandemic death and hospitalization and can potentially decrease the risk of other complications like long covet misd neurological effects diabetes and hepatitis we need to protect our children without further delay thank you for your time thank you the next speaker is tamara thompson you have three minutes good afternoon members of the committee and thank you for allowing me to address you again today i have no financial conflicts my name is tamara thompson and i am an attorney who represents children as well as the mother of a five-year-old boy and 23 month old girl yesterday i urged you to recommend authorization of moderna for the older pediatric cohort and am thankful that you did i also urge you yesterday to do the same for the youngest cohorts i am here again today to request that you vote to authorize both moderna and pfizer for the youngest age group so that our littlest americans can have access to these life-saving and necessary measures of protection against severe outcomes disease and death from covet 19.
i spoke yesterday about how important this authorization is to me and my family and how long we've waited to protect our sweet girl she is actually one of the data points you saw in modernist presentation today as we joined the trial in february today i want to address how important it is that both vaccines are authorized for other families in my social circle i have heard from many other parents that they are desperate to vaccinate their children under five they thank me for my advocacy and tell me how exhausted they are and how very hard it has been to feel left behind and with no measures to protect their young children from the threat of covet 19 referring to both the acute threat and the possible long-term harm of infection after infection with stars kobe 2.
long covet is a threat to children and adults alike like me other parents have pulled kids from daycare during surges and work their full-time jobs from home while trying to parent babies and toddlers they've also gone through interruption after interruption of care with illnesses exposures quarantine and isolation some parents are not able to work from home at all and don't have the ability to pull kids during surges but must take unpaid time off when exposures and quarantines occur i have heard over and over again that it is exhausting and it's been even more difficult since the rest of the world have moved on dropping on non-pharmaceutical interventions because they quote have all the tools we don't have the tools not for our little ones and therefore not for our family it is essential to authorize both vaccines right now because there are advantages to each series that will help families in different positions for example we see greater efficacy and immunobridging in just two doses of moderna versus two doses of pfizer vaccine which would allow rising kindergarteners to achieve more protection before starting school in september at the same time while pfizer's n in calculating efficacy is low and confidence interval wide it may be that its three dose scheme provides greater efficacy in the long term in addition having two vaccines for this age group available will help in ensuring better access a stronger supply chain and a choice for families who have waited so long for protection we need options we need access we need to make sure this group crashes up to older cohorts in terms of variant specific boosters and up-to-date preventatives and treatments as we heard dr fauci say in april of this year all of the stuff you hear about kids let them get infected is a bunch of nonsense please authorize both the moderna and pfizer vaccines for them today thank you for your time and dedication to the scientific process thank you the next speaker is mr sam dalton you have please please hello my name is sam dodson i run a podcast called to the lifeboats and i have no relationship with the pharmaceutical cartels i've schooled in electrical engineering and two years ago i'd never heard of mrna but let me tell you what i've learned since it starts with the shot you told us stays at the injection site we know it doesn't you knew it didn't bio distribution studies show that it goes to every major organ primarily the heart liver and spleen where thanks to the highly inflammatory lipid nanocomplex it transfects the cells that complex contains a pegulated lipid being mass injected into humans for the first time ever while the animal studies showed heart attacks in pigs after the second injection you knew the lipid nanocomplexes collect in the ovaries where they have the potential to cause devastating effects on reproductive health yet you did nothing when women started complaining of menstrual problems you did nothing transfected cells in every organ pump out the spike protein that ends up in the nucleus where it interrupts p53 line one and brica you didn't know this because you didn't care to ask the question and when shown to you in a study you did nothing every transfected cell expressing spiked protein risks autoimmune disease the most acute of which is myocarditis when people started dying of myocarditis you did nothing the spike protein floats freely in the vasculature finding its way into the brain breast milk and the environment as the body sheds this protein in exosomes making those around the vaccinated sick the spike protein directly affects toll-like receptors and cd4-t cells which are essential to the immune defense against these very viruses when the vaccinator repeatedly caught covet and suffered reactivation of herpes shingles papilloma virus and unprecedented numbers you knew this was a massive problem yet you did nothing you knew that the mrna stays around for months in lythnode germinal centers causing t cell exhaustion because the stamper group performed the study that you couldn't be bothered to do and then you ignored that massive safety signal you were warned about encompares and the effect on p53 yet you did nothing when you were warned about prion disease and amyloid as a result of the huge amounts of spike protein produced by these therapies you did worse than nothing you silenced those people who raised the alarms you were informed of fraud in the vaccine studies yet instead of investigating you colluded with the manufacturers to suppress trial data for 75 years knowing all of these concerns you now want to inject the very young who have zero clinical risk from covid and for which not one single study has shown any clinical benefit you have abjectly failed in your sole duty to ensure the safety of any drug given to americans the late francis oldham keisley would have been ashamed at how you've turned a once respected agency into a corrupt corrupted vessel for the very corporations you swore to protect the american public from if you have one shred of humanity left you will recommend an immediate halt to all the shots and pray that god has mercy on your souls you might also want to figure out how we're going to diagnose myocarditis in very young babies who are unable to speak thank you thank you the next speaker is donna you have three minutes hi thank you my name is donna i'm grandma to two-year-old liam and a licensed family daycare center owner operator i have no conflicts please take a moment to picture your life right now if you weren't given access to even one covered vaccine dose yet two and a half years after this began now think about going into a small room with 20 other unmasked unvaccinated people eating and napping in close contact spending up to 10 hours there every weekday this is the scenario parents are forced to put their unvaccinated children in every day and is what is why i implore you to approve a vaccine for children under five today kovitz seeks out those who are unvaccinated the convoluted path to approval these trials have taken have left the youngest of our society most vulnerable the repeated reassurance that a vaccine would be available in the coming weeks or months has not brought hope to families but rather frustration and despair when these claims did not come to fruition the truth is families have gone to extreme lengths to protect their babies because children are getting very sick and dying of covid19 the fda should strive to be nimble and able to pivot quickly as the virus changes if the rest of our country can choose a vaccination and subsequently drop any and all mitigation measures before all vulnerable populations have protection then parents deserve the right to choose a to vaccinate our children and to choose between moderna and pfizer we need a comprehensive plan to ensure this age group has access to up-to-date boosters and future variant specific vaccines at the same pace as all other age groups our governmental bodies need to do what is necessary to ensure our children are not denied life-saving vaccines for two and a half years during the next pandemic when you cast your vote this afternoon please remember these small children and vote to approve both moderna and pfizer vaccines for children under five so that they have some protection with reduced risk of severe illness caused by coven 19.
thank you for your hard work throughout this pandemic and for giving me the opportunity to share my views thank you the next speaker is katherine deal good afternoon my name is catherine diehl i'm a mother of two-year-old twins and a phd in philosophy with a focus in medical ethics i have no financial conflicts i am here today to strongly urge the committee to recommend authorization for both vaccines the question before you for each vaccine is whether based on the totality of medical information available its benefits outweigh its risks the data presented today and real world information collected over the past two years demonstrates the answer to this question is a clear and resounding yes to evaluate the benefits we must follow the standard of probable improvement employing the tools of bayesian analysis supported by the fda's own guidelines these vaccines very clearly meet this standard we're better we thought we're better off with them than without them the standard must guide our action rather than any arbitrary statistical cutoff such as requirement of 50 efficacy against symptomatic illness such a standard would be additionally inappropriate in the context of current variants when attention has shifted to protection against severe outcomes including hospitalization and death evaluation of these vaccines does not occur in a vacuum rather it occurs in a context in which these vaccines have proved to be safe and effective in adults as well as in a slightly older age cohort this background should inform our priors that is our starting point in our considerations here the success of both trials in meeting immunobridging without any safety signals allows us to update these priors in light of positive evidence following the standard of probable improvement lets us infer from successful immunobridging is highly likely the vaccine will be similarly effective in the prevention of severe outcomes like hospitalization and death in children under five the safety record in older cohorts and absence of safety signals in the trials also reassures us that new safety issues are not likely to crop up once vaccinate vaccine distribution commences to the broader population you have seen compelling evidence in both companies documentation that the benefit risk analysis is favorable based on acute outcomes but there are additional factors that speak in favor of approval covenant infection carry substantial long-term risks our understanding of these long-term implications is evolving and here that the methodology i have described is particularly helpful to ignore the growing evidence lasting cardiovascular damage new type 1 diabetes diagnoses brain atrophy vascular amyloid deposition hepatitis and so on merely because we have yet to accumulate a decade's worth of high quality double-blinded randomized control trials and meta-analyses thereof would be dangerous and irresponsible these vaccines are likely to reduce such effects in two ways first by preventing some portion of infection they reduce the number of cases in which long-term damage can occur second numerous studies have suggested that breakthrough infections are less likely to lead to long covet again this must be factored into our analysis as a philosopher and a parent i urge you to approach your decision with these methodological principles in mind and reach the conclusion that both vaccines should be approved thank you for your consideration and thank you to the families of these trials who have made this possible thank you the next speaker is jessica neri good afternoon i have no financial conflicts of interest i am a mother of two amazing children my daughter is six and my son is three i am speaking today to advocate for children under five years old and their parents who wish to have the option of vaccinating these youngest children since most masking mitigations have been lifted children under five have been sitting ducks for covid without protection while vaccination has been enthusiastically recommended to every other age group we have been through six waves of covid now including the current surge with no protection for our most vulnerable children the children three and over that can mask are obviously not wonderful at it and the children under three have absolutely nothing at this point to protect them from severe and sometimes fatal outcomes based on real world data in persons 5 and above it can be safely concluded that moderna and pfizer's vaccines for our youngest children offer excellent protection from hospitalization severe illness and death i am frustrated that this process was stalled with moderna since their studies were nearly complete in december when an expansion was requested by the fda parents still long for a clear explanation regarding the reason for this expansion which was requested during the largest covet surge of the pandemic one that resulted in thousands of children under five hospitalized it is upsetting that a safe and effective vaccine has not been prioritized especially with so many americans getting back to their normal lives resulting in our children being placed at even higher risk of infection in the past two years my husband has worked in nursing homes schools restaurants and churches as a union hvac service tech he has chronic asthma and has been wearing a mask for years at this point just to protect himself and our family until we can all be vaccinated i have put off doctors appointments these past two years for a pre-pandemic health issue because of the fear of bringing the virus home to my son and daughter before they have been vaccinated parents like myself are frustrated that we are not being seen we believe in science and the process of trials evaluating data and the health agencies involved in managing all of these aspects but moving forward i would hope this age group doesn't get left behind again i would like serious thought given to the possibility of running trials for future treatments and vaccines of all age groups at the same time so our youngest children are not forgotten relevant agencies need to work with state and local governments to facilitate a rollout that's truly fair and equitable for all kids under five and their parents parents like myself just want the choice thank you for giving me the time to speak thank you the next week is uh katherine uh lingling lindy you have three minutes thank you for this opportunity my name is dr kat lindley i'm the member of the steering committee of the world council for health i have no conflicts of interest cdc data from february showed that about 74.2 percent of children have had coveted already over 150 studies show that natural immunity is superior the infection fatality rate under 5 years of age is 0.1 in hundred thousand or one in a mil in a million the risk of the shot in the already noon is higher than one in a million both pfizer and moderna express expressly eliminated those that were naturally immune from their studies they did this to avoid the hyperimmune response and possibly death vaccinating the already immune puts them a serious risk for having a hyper immune response that means you will be voting for some children to have a severe adverse reaction and possibly death if you vaccinate the already immune this is bad medicine there is zero reward only risk these vaccines are not medically necessary or clinically indicated bears show children ages birth to 18 who have been vaccinated with pfizer and modernist vaccine have had severe life-threatening adverse reactions such as myocarditis liam beret seizures and more severe adverse reactions of death article by house and all that was published in may 22 of 2022 in american academy of pediatrics shows myocarditis 2.2 per million cases features 7.6 per million cases i will share two cases seen by my colleagues 14 year old male double vaccinated advisor vaccine has recent history of chest pain on reduction initial echo and ukg were normal proponents 22 000 increasing to 48 000 in six hours cardiac mri with gadolinium show transmural enhancement consistent with myocarditis case number two thirteen-year-old female first fighter those last august had first seizure within 30 days got a second vaccine in december had another seizure then has a third booster and now has scored to six seizures a day she was an active soccer player and a good student now unable to play sports or attend class in person we have no long-term safety data in any of these studies the risks clearly outweigh the benefit the verse reports 28 312 deaths so far in all age groups when will we say this is enough what is the magic number that will make a cutoff and stop pushing these vaccines is it fifty thousand hundred thousand million when do we uh say that we cannot give this to our children their uh recovery rate is over ninety 99.99 eight five percent these are healthy children and the risk does not outweigh the benefits these vaccines are not medically necessarily indicated thank you for your time thank you then last season for the session is caroline bishop you are pleasing it hi thank you my name is dr caroline bishop and i'm an associate professor of classics at texas tech university i have no financial conflicts of interest i'm here in my capacity not as a professor but as a mother to urge you to approve both the modern and pfizer vaccines for children under five today i wish to share with you the increasingly punishing links i've had to go to in order to keep myself and my 14 month old daughter free from covet as we've continued to wait for a vaccine i could talk about the difficult decisions we've been forced to make along the way cancelling our daycare during the delta wave and keeping my daughter at home with me while i was technically on a harvard funded research sabbatical to write my second book never having gotten to take her to a museum or to visit her cousins or to a playdate being able to count the time she's been in the grocery store on one hand but instead i'm going to focus on the fact that i've had to be a solo parent for the past month or so watching my daughter full time never leaving the house while also feverishly writing a conference paper that i have to deliver this friday during naps and after bedtime has been one of the most challenging experiences of my life why have i been doing this because my husband who's a trial attorney can no longer wear a mask in court part and parcel of the countrywide removal of all mitigations at a time when we're seeing one of the worst coveted surges yet as cases began to grow in our area he made the heartbreaking decision to move out to our guest house at the time we'd hoped the committee might meet to approve the modern vaccine on june 8th and when the meeting got scheduled for today our hearts broke a little more this past month i've been desperately holding on for my daughter to have the protection against severe outcomes that both the moderna and pfizer vaccines have been shown to provide i've been lonely and alone devastated when my husband missed our daughter's first steps i know he feels devastated too he has to hear her call out dada when she sees him in the yard and know he can't cuddle and play with her she's always so delighted to see him and doesn't understand why he won't horse around with her like he used to do we didn't publicize this decision of ours only a few close friends know that's because even among our highly educated friend group almost everyone is acting like the pandemic is over i spoke to you yesterday about the special kind of heartbreak you feel when you see people you love like and respect start to act with absolutely no concern about the fact that your child has no protection against covid today i'd just add that it's both disorienting and maddening to see almost everyone living like it's 2019 again when you're still stuck in march 2020.
however i can now say with certainty that my husband and i made the right decision hard as it might have been how do i know because this past friday he came home from work with a sore throat and as i'm speaking to you he's sick with covid fortunately he's vaccinated and boosted with moderna and his case has been mild my daughter deserves that same protection you have the ability to give it to her and to reunite our family for myself and for the many parents who didn't have the privilege to isolate like i've done i'm begging you to approve these vaccines thank you very much thank you that completes the open public hearing session and i would like to hand over the meeting back to our chair dr mato take it away for the next question excited on the agenda thank you uh and thank uh i thank all the participants in the open public hearing we really do listen to what you have to say to us we now return to the question and answer sessions we will first deal with the questions and answers about the bondurne vaccine and these questions can be for the fda presenters or the sponsor presenters we have a relatively short period for the question and answer sessions 25 minutes after which we have our own internal discussion so remember there's that session as well and following that the vote completing the action on the modular vaccine so we're completing the action on the modern vaccine okay doctor you see if i've got the full list in front of me here dr berger followed by dr perkins hi thank you all for the earlier presentations i you know i had a question based on fda's briefing document that was applied uh and specifically it was the um two tables looked at the subpopulation analyses i'm specifically looking at the uh you know the vaccine efficacy in children who are obese i i noticed that the vaccine efficacy rates for the six to 23 months olds were negative 5.6 and 2 to 5 year olds were listed at negative 15.4 and fully recognizing that confidence intervals and these were huge um just wanted to get a sense of like whether because i didn't see this listed in the uh you know in any of the post approval examinations what kind of what kind of data are you currently collecting on children who are obese to understand the efficacy there or to at least dive into this signal a little bit more um so so i believe that was a question for me but if i'm wrong please correct me so i think the question is about moderna and how we follow up on the efficacy rate in children who are obese and um so as you mentioned we have some efficacy data uh from the original clinical trial um however those data right now are relatively small subgroup of the overall property and so the way in which we will be moving forward to follow vaccine effectiveness would be actually in the long-term effectiveness study that have ongoing in southern california so in that study we are able to enroll hundreds of thousands of individuals and we actually are parsing those analyses by specific risk groups i can show you the immunogenicity in the young children so if you can please put up slide im23 for me oh give me a second i gave the i gave it to the wrong uh i gave it to the wrong share so modernist give me one second um actually i know you should have the right share right now unless you want oh you moved it there hold on one second and take it away you got it okay there we go and then i'm just going to say that i'll want the slide in a moment for the six months to 23 months so what you see here are the geometric mean titers and associated 95 confidence intervals for the children who were two to five that received mrna 1273 and you also see the respective gmt ratios and this is again versus the adult population i need to note again that the sample size of the children who are obese is relatively will require further follow-up and then if we can put up the next slide which is im24 we'll see the infants and toddlers and so here we see gmt ratios of 0.9 to 1.4 again sample size is relatively small so wider 95 confidential intervals than those who are obese but overall greater than 1500.
thank you thank you dr perkam followed by dr sawyer thanks i had a question for the sponsor um i didn't get to ask this question initially when you presented your data you had a fairly large study population in the phase 1 trial that got the higher dose of the vaccine and similar to what i asked pfizer is i'm curious did you see a dose-dependent response in that that higher dose compared to the lower dose that you ended up choosing and then as a second question to set up that's some somewhat relevant is in your post-marketing studies that are planned and there's no discussion of the immunosuppressed population and as we have seen in post-marketing immuno-suppressed populations have received an extra or a third dose as they primary series and i'm curious if if there are studies planned for moderna for indiana suppressed children to specifically address this question yup thank you for that so what i would like to do is address your first question first which is the comparison of the 25 microgram and 50 microgram which are the doses that we investigated in this trial and so uh could you please project a8 sorry that's alliteration but um two a's and an eight there you go thank you um so what you see um in in this slide is uh the young children and you had asked about a dose response so we do see a dose response um with a higher dose and we saw gmt ratios in the initial part 1 population of 0.8 and 1.4 respectively we were also looking at the safety profile at the time made our recommendation to a data and safety monitoring board and they in fact confirmed that we they agreed with our selection of the 25 microgram dose in the children two to five and because we selected the 25 microgram dose then we did not go up to 50 micrograms in the youngest babies and then um your second question for me is with respect to immunocompromised children and so um we have already committed to doing um in europe uh um immunocompromised trial and in fact we were waiting until we had selected the dose and had confirmation that that dose was safe and effective in uh healthy children before moving to the immunocompromised population and of course we'll be studying a three dose schedule as we're administering to adults with the selected dose thank you very much appreciate that dr sawyer followed by dr kim where are we up to yeah dr sawyer thank you dr monto so it appears that fever is occurring at a significant rate which is something we see with other routine childhood vaccinations but the pediatricians in the group have certainly lived through the experience of seeing enhanced fever and even febrile speakers with co-administration of other vaccines together that all caused fever dr chatterjee brought up this question earlier and the sponsor replied that they are planning some co-administration studies my question is for fda are such co-administration studies required for a full bla or is it up to the sponsor to just decide how much to study that question and or do we need to wait for post marketing or post authorization studies to really get a handle on that question thank you for that that question um thank you dr fink i think you're best ready to handle that um i will answer that so um we we have routinely requested co-administration studies in licensure applications of vaccines that are intended for the very young infants you know those who are younger than six months of age because the immunization schedule is is so compressed and it is difficult to to avoid co-administration we have not routinely requested or required co-administration studies for older children but we have always encouraged vaccine manufacturers to study safety and evaluate for immune interference of co-administration when introducing a new vaccine into the pediatric schedule and we do expect that studies will be done going forward looking at this thank you thank you dr kim followed by dr ganz well thank you very much um on the topic of primary series and booster dose uh this uh i think the the committee has has discussed this on several occasions um but on on that topic for modern vaccine um the definition of primary series is to those and you're currently working on on a study to to evaluate the the impact of the third dose and it's it's on that third dose that i'd like to ask you if you have any preliminary information or if actually you can if you can share with us uh some some of the um some of the characteristics of the study design and and the possible impact and perhaps your hypothesis and how that might influence uh your definition of primary serious versus uh versus booster dose yeah so um i'll speak a little bit about um the boosting that we're planning in each age cohort um we we don't have uh hypotheses to define two versus three dose series but as i mentioned we've heard your feedback about that but in terms of the third dose booster we in adolescence we asked them once we saw the incidence rates climbing after omicron as we discussed yesterday and those data actually we are anticipating momentarily and we'll be sharing them with the fda once we have them compiled that will be the the first group then in july we will be getting the data from the six to 11 year olds so the six to 11 year olds were followed primarily um through delta their uh the longer term follow-up cohort is now mostly the mrna 1273 cohort because of the uh authorization of another vaccine and people going to get vaccinated so we'll really see um just primarily what that third dose booster looks like um in that cohort that will come in july and of course we'll share those data when available and then the youngest children actually based on other feedback we received from this committee we tried to keep the blinding in place as long as possible to have as long of double-blinded efficacy follow-up as we could i think once a decision is made and one or more vaccines hopefully will be authorized we will be unblinding and then offering that third dose at least three months after the second dose and that three-month interval is really defined by an interval that we've seen from dmid so cmid assessed heterologous boosting with that three-month interval afterwards and you know as you mentioned there may be some safety and immunogenicity benefits to to that interval so we will share those data when available and then we have mrna 1273 and we have some clinical supply with an omicron containing variant and so there will be some of the cohorts in the youngest kids uh receiving the omicron containing variant and um that really is to bracket the booster responses so we'll see the omicron data that we'll share with you in two weeks in the adults and then in these youngest kids the omicron containing variant and we believe that will really help give the cumulative picture of the capability of the vaccine thank you very much a very broad response to a broad question dr ganz followed by dr rango thank you so much and i really appreciate everything all the thought that you've put into what you will be doing moving forward and so my question really for the fda and i don't know if doran think is available but um i'm impressed with how much there is after uh already predicted to be available to the fda and my question is before moving on to licensure will there be availability of the data to be reviewed by the committee and maybe even some recommendations moving forward thank you um i think fda always makes a a case-by-case decision on uh seeking input from the vertac depending on whether we consider there to be important questions about about benefits and risks that would would benefit from or require input from from the verb pack i think as you as you know we have taken certain actions uh without a verb meeting when we felt that those actions uh needed to be done expediently or uh when we felt that the very most pertinent issues regarding benefits and risks had had already been discussed and there was nothing new to discuss and so we will we will consider those factors uh before we take uh any future action on on a case-by-case basis you my question to moderna is are you going to be looking at immune correlation any of your studies moving forward because we seem to be stuck on looking at neutralizing antibodies which we all know for viruses while um show you some correlate that is there in the immune system is not necessarily the correlative protection for these respiratory viruses yeah so this absolutely is an area of interest for us we have published our work from the ancestral strain which dr dos discussed a bit with you yesterday and we're now speaking with our collaborators at the covpn and then also at the nih about now how we might take those uh results as we're getting the omicron neutralization titers and omicron cases and work on an omicron correlate of protection so i think our feeling is that probably omicron is the next most important variant to investigate and so we're discussing how we might do that now that we're so distant from the original blinded trial but it's definitely in there thank you very much moving on to dr rheingold followed by dr nelson question after that we're falling behind schedule dr ryan thanks very much i'll try and make it quick so first mark sawyer asked my question about co-administration but the other question i have you know for a lot of routine childhood immunizations uh there isn't much circulation of the agent in the population so we're not typically faced with the problem of administering the vaccine to a child who's recently been infected uh we already have antibodies and clearly with covert 19 that's not the case and you may have shown these data but in terms of reactorgenicity uh either with it coexist with the pre-existing antibody or recent documented covid19 is there any reason that the safety profile would be considered different this presumably will be an issue for cdc if the vaccine is given eua what kind of clinical guidance they give about either delaying vaccination or proceeding with vaccination under different circumstances thank you yes um we actually do have the safety data uh by seropositive and pure negative adverse events so if you can put the slide up please it's sy23 thank you so what you see on this slide are the children who are two to five years of age in children that were sars kobe 2 positive at the start of the study in black the ones that were sars kobe 2 negative the rates were relatively comparable between those two subgroups if there was a trend that we noticed it was that uh systemic rates of reaction tended to be higher after post those two um in the initially sierra negative children as opposed to post-dose one which was more frequently observed in the zero-positive children um and then uh let's also put up the data for the intervention oh sorry no i just wanted to show you um for the other age group what the data look like post those two and post-dos one for the uh zero positive and sero-negative children thank you okay thank you dr nelson followed by dr fuller who will be the last questioner in the session yeah so i just had a couple of quick questions i know we're falling behind and one has to deal with the subpopulations of blacks who are enrolled in your current study so i did note the overall low enrollment at 3.2 percent 4.7 percent i'm sure there were many challenges in getting a higher percentage but i also noted with interest the higher immunogenicity or humoral immune response the one was consistent with the older age groups you did with the data you presented yesterday and in particular the six to 23 months it was almost twofold higher than the the white population or other populations so one one question i have for you is this a real distance are we victims of small numbers is there some significance to the trend of a higher immune response that you're seeing with the black participants and then the second question just to prime you is with respect to the immunogenicity data set as a whole is there any evidence of possible over-representation from individuals with higher titers either of black rays or perhaps even post baseline infections yeah thank you for those questions so um let me first put up the slide looking at the immunogenicity by race so those slides are uh if you guys can find sy 31 there we go oops put the slide up please uh i just saw it michael i don't know okay why don't you discuss it there we go okay okay there we go so um these are the children two to five the pattern um uh is similar in the youngest infants in the interest of time i'm happy to show it but i understand we're short of time so um as you mentioned the immunogenicity cohort which is of course a subset of the total cohort um there were 20 african-american children and their titers were higher but the 95 confidence intervals overlapped and in terms of representation in the trial i think we didn't see over-representation of groups that might have had reason to think that there were higher titers so you see the proportion of the groups that had the highest higher in terms of race and certainly in terms of zero positives they were much less frequent than zero negatives and i can show you in the toddlers as well if you want to see or if you want to move on it's up to you i think we can move on dr fuller final question i just i just wanted to follow up on the earlier question i suspect that you're going to be looking at those things in the future but my concern is that the the one child that um that had the seizure was there any underlying thing like sickle cell or asthma or anything that could be detected because even though there only may be one uh if that's someone's child that can identify that they have a risk factor that would be very useful to know yeah dr fuller um so we don't really have other medical history on that child they were previously well um i will say and i i'll just add maybe for um reference as a pediatrician febrile seizures often happen in children who are healthy with no underlying condition so they occur at a rate of about three percent between the ages peak ages of of one to five so it didn't necessarily surprise us that this was a child who had no otherwise underlying condition so did you look at things or will you look at things like sickle cell or or that sort of thing in the future i heard you mentioned immunocompromised earlier yeah no so um the the trial um in the immunocompromised is going to be specific in standalone the power of our large effectiveness study in a diverse database like kaiser southern california really allows us to look at events by different different underlying conditions allows us to look at different age groups and so forth and so certainly here the interest in seeing what the effectiveness looks like in children with sickle cell so we will look into that right thank you and thank you to the sponsor and to fda for their answering our questions we now move on to the discussion of the voting question and the vote and what we're going to be doing as usual is having the committee discussion over the voting question we will then vote and then we will have explanation of votes for those who wish to explain their votes so do we have the voting question we're going to be discussing based on the totality of scientific evidence through the benefits of modernist covid19 vaccine administered as a two dose series outweigh its risk for use in infants and children six months through five years of age discussion dr meisner followed by dr portnoy thank you dr monto um i um like to make a um a couple of comments of the regard to this i i don't think anyone could listen to the public the open public uh hearing session without being troubled by the diversity and the the emotional commitment that's been put into this in issue of immunizing children um between six months and and five years i i uh it was quite moving i um i my my personal feeling is that it would be hard not to uh include uh six months to uh uh five years of age in an amendment to the eua in view of the strength of the data that we have seen today but i would like to make this comment and i think it's very important as dr cohn said yesterday that the communication or the messaging be made as clear as possible for parents to understand the relative risk and the relative benefit i think we for example we heard we've heard several times that there were approximately 442 deaths so far in the pandemic among children less than 5.
so that means about 220 deaths a year approximately if you look at the number of people who are struck by lightning in the united states on a year it's 270. so we're talking about a very rare event if we talk about hospitalizations among children between six months and uh five years of age the hospitalization rate on the cdc website the latest site is 2.3 per 100 000 or uh 23 per million and there are about 20 million uh children in this age group so 20 times 23 is 460 hospitalizations associated with covet in in this age group that we're considering today and probably only a fraction of those are because of ovid 19 infection rather than a coincidental association so really we'd be talking about vaccinating close to 20 million children in order to prevent two or three hundred deaths and it's a matter of how an individual weighs the risk and benefit i think the vaccine should be available for certainly high-risk children and for families that are so concerned they are troubled by that risk ratio and they should have access to the uh to the vaccine but i again feel very strong the parents should understand how small these numbers are the very low risk from the vaccine but it's also a very low risk from the infection itself and i think that has to be communicated clearly to parents so they can participate in the decision about vaccinating a child in this age group thank you thank you dr portnoy followed by dr berger great thank you i've really enjoyed this conversation and i have to say i was extremely moved by the public comments as well nobody can not be moved by it but i work at a children's hospital and i remember earlier this year walking by the emergency room and looking in and seeing that the place was completely filled i asked one of the security guards what's going on and he said well it's coped emergency room was was filled our hospital was loaded up with children who had coveted now i know that the death rate from covid and young children may not be extremely high but it's absolutely terrifying to parents to have their child be sick have to go to the hospital or even go to the emergency room or their primary care doctor because they're sick and having trouble breathing so this is it's not just gaps we have to understand how distressing this is for parents whose children are affected by this disease every pediatrician that i know at our hospital has been waiting eagerly for this this vote to occur because they can't wait to start giving this vaccine so our question today is is the benefit outweigh the risk of this vaccine and i think that the evidence is pretty clear for preventing severe disease hospitalization emergency visits this vaccine is very effective it's also very safe to use i'm a little bit disappointed that it doesn't prevent infection by covet as effectively as it could because that's what spreads it around but you know even in adults we can't prevent infection but at least we can stop people from being terribly sick so this is a long-awaited vaccine i feel the pain of those who are opposed to it have had bad experiences with it they can choose simply to not get the vaccine but there are so many parents who are absolutely desperate to get this vaccine and i think we owe it to them to give them a choice to have the vaccine if they want to thank you thank you dr berger followed by dr fuller thank you as well and i i i was going to say something similar to what dr pornoy was was pointing out is you know it's not just about death it's about how we're preventing hospitalization and you know i think some of the you know really distressing information that we've we've heard is that a quarter of those of those children they're going to the hospital are ending up in the icu and 63 of them you know have no 63 of them have no underlying comorbidity to actually be directing this and so you you have to ask yourself like what other you know those that do have comorbidities might be at a higher risk and so it really is about giving a choice um but yeah i actually had a question about the question we're being asked and part of this is just that the framing you know all the data we've been given and specifically the way it was collected was dividing up the six months to 23 you know month-olds from the two to five-year-olds and yet the question is putting them all together now this may not change the outcome but you know just it occurs to me that it's sort of an oddity in terms of the voting question itself that we're being presented with because the data isn't exactly aligned 100 across both of those groups you know there are there are slight differences in vaccine efficacy and some of the some of the side effects we've seen may not be significant but i did have a question for fda as to why it was combined in the voting question as opposed to having it be separated into those two different age groups for voting we have an answer from fda dr pink yeah i so the the eua request from moderna was for emergencies authorization of the 25 microgram dose level for use in uh the age group of six months through five years so that that is why the voting question is constructed accordingly we yesterday dealt with two separate eua amendment requests one for adolescents one for ages six through eleven and that's why those questions were constructed accordingly i do recognize that that the data was presented according to the two uh smaller age groups within uh six months through five years and for advisor it was done the same but i would hope that the committee would really focus on the similarities and if they uh and consider the age group as a whole and if they feel compelled if any community member feels compelled to have a different opinion for one smaller age group versus another then of course you can you can raise that concern thank you and i am reminded that this is a discussion right now we will have a second session after the vote in which you can explain your vote so technically you're not supposed to say how you are voting at the moment but you can say whether you support or not the approval dr fuller followed by dr reingold yes that is what i was going to say that the need for clear messaging to parents and guardians about the choice for having the vaccine or not um is very important and that the follow-up studies that are planned are very important um the benefits seem to clearly outweigh the risk particularly for those with young children who may be in kindergarten or in collective child care so that those who want to do this will have that option uh but i would ask should this pass or should this be recommended by fda and by the advisory committee and passed by fda and cdc that parents really consult their pediatrician for their children my question earlier wasn't just for sickle cell but any other unknown underlying condition that might impact the outcome so this is a decision that parents and grandparents and guardians will have to carefully way should we should this actually go through thank you dr reingold followed by dr sawyer so so thanks um you know one of the speakers in the public session urged us multiple times to think of the children now i think he and i might think of the children in slightly different ways but but you know my way of thinking about the children is that if we have a vaccine whose benefits outweigh the risks that making it available to people is a reasonable choice i would point out that we as a country continue to give a large number of vaccines to children where the risk of the child dying or being hospitalized of those diseases is pretty close to zero those include polio those include measles we vaccinate large numbers of people against hpv even though very few of them would ever develop cancer related to hpv so we with our vaccines are trying to minimize serious illness and death or perhaps reintroduction of something like like polio into the united states but but we we generally know that many of the infections that we are vaccinating against uh the the serious outcomes are quite rare actually um and and we nevertheless try and vaccinate a large part of the population if not everyone so i think we do need to focus on the serious outcomes and even if they're relatively infrequent and even if a vaccine is less than 100 percent effective flu is another good example we we continue to recommend flu vaccine for people even even though it only made 30 to 40 effective um and so if we have a prevention opportunity i believe we should take it but just one last caveat my personal preferred wording is not to tell people that something is safe i think that's the wrong messaging i think nothing in life is perfectly safe no drug no vaccine no personal choice to get on a plane or get into a car is quote safe i think what we need to emphasize is that the benefits outweigh the risks thank you thank you dr sawyer followed by dr levy first of all i'm generally in support of approval for many of the reasons that have been outlined follow up dr reingold's comment i would like to add to the benefit column the fact that as we heard in the public comment some parents are so concerned about the risk of exposure that they're still completely isolating their children so socially perhaps above and beyond what the current cdc and aap guidelines suggest and the potential adverse impact of that isolation was brought up also in the public comment session so the availability of these vaccines will liberate those children to some extent whose parents will find relief and and feel a little more comfortable to let their children start to socialize in the appropriate environment the other potential benefit that's been touched on is the impact on long covid which has further potential challenges for development as we learn more about what long cobit does and what the implications are for school performance so i think we there's a lot in the favor in favor of the benefit column in the risk benefit equation thank you dr sawyer dr levy last question so far thank you i am generally supportive of this direction and i also want to emphasize the importance of knowledge and that we keep building on our knowledge we saw a lot of good information today including some immunogenicity information but as i mentioned yesterday we have a ways to go to understand the correlates of protection against coronavirus antibodies are likely very important but not the whole story we'd like to see t cell data we'd like a recognition that correlates may be age specific you might get a similar antibody response at a given age but antibodies act in a context together with the complement system with phagocytes and those systems might be distinct by age due to immune ontogeny so i encourage fda and the sponsors to continue to develop more sophisticated and nuanced information about correlates of protection the other key here will be safety surveillance uh the possibility of febrile seizures particularly in in those unusual cases where there's a high fever after the vaccine and the young age groups it's possible we'll see febrile seizures that this gets pushed out if indeed that's the determination by fda so we have to keep an eye on that and also potential impact on other balance of other respiratory infections is what it was alluded to uh by fda by dr doran fink so those are areas that i think where knowledge uh it needs to continue to evolve but overall i'm supportive it's a bioethical concept of a presumption of inclusion we have reasonable safety data and this vulnerable population should be included and there's a broader context this platform this mrna vaccine platform may be useful not just against this current coronavirus and its current variants but the next ones as well as future pandemics thank you thank you dr levy that concludes the questioning i mean the comments concerning the voting question we will now have the vote and then we will have explanations from those who wish to explain their vote further thank you dr monto only our 10 regular members and 11 temporary voting members a total of 21 will be voting in today's meeting with regards to the voting process dr munto will read the final vote in question for the record and afterwards all regular voting members and temporary voting members will cast their vote by selecting one of the voting options which include yes no or abstain you'll have two minutes to cast your vote after the question is read and please note that once you have cast your vote you may change your vote within the two-minute time frame however once the poll has closed all votes will be considered final once all the votes have been placed we will broadcast the results and read the individual votes allowed for the public record does anyone have any questions related to the voting process before we begin okay okay dr mata if you could please read the voting question record for the record based on the totality of scientific evidence available through the benefits of the modernity 19 vaccine when administered as a two dose series 25 micrograms each dose outweigh its risks for use in infants and children six months through five years of age okay please pull up the voting pod at this time you may start to vote okay it looks like all the votes are in we can go ahead and close the pulp pull thank you okay there are a total of 21 voting members for today's meeting and the vote is unanimous we have 21 out of 21 yes votes zero no votes and zero abstain votes okay i will now read the specific votes for the record dr berger yes dr nelson yes dr fuller yes dr levy yes dr monto yes dr sawyer yes dr offit yes dr reingold yes dr bernstein yes dr mckinnon yes dr wharton yes dr pergam yes dr chatterjee yes dr portnoy yes dr lee yes dr kim yes dr cohn yes dr marasco yes dr meisner yes dr hildreth yes dr ganz yes and that completes my reading of the vote and i will hand the meeting back over to dr montan now we will proceed to explanations of the vote from anybody who wishes to speak dr hildreth thank you dr uh i think the evidence that we had in front of us justify the voter yes but i did want to make a point that i made yesterday that dr majna made a few minutes ago we got to be transparent about the real risk of coca-19 for children tens of millions of children in this age group have been infected and have done just fine i think we need to make parents aware of what the real risks are and let them make decisions but for those parents who choose to do so especially those parents of the kids with underlying conditions this is a choice they should have and the police are going to have it thank you thank you dr portnoy and thank you as a designated consumer representative member of the committee i can speak on behalf of the patients that i take care of i know that there are a lot of very relieved parents almost certainly who are listening to this right now they've been waiting for a very long time i can't again want to emphasize how terrified parents get when their children get sick even if they don't die from it i take care of patients who have food allergy the number of deaths from food allergy is extremely low and yet the parents are terribly anxious and worried about this disease covet actually causes a lot more deaths i understand why parents are very nervous and fearful of doing normal activities and especially if their child actually catches kova but even the fear that they could catch covet this will certainly alleviate a lot of their concerns and so i'm really happy that the vote went the way it is i think it was the right vote thank you thank you and dr nelson thank you dr monto i do believe the benefits far outweigh the risks that were involved and personally i really do believe this recommendation does fill a significant unmet need for a really ignored younger population in need of options families will now have choice that they did not have before and i fully believe in the intelligence of families to make the right choice for their family and children particularly when we provide clear recommendations with respect to the information we have on hand regarding the risk and benefits my personal hope that every child in the u.s seeks and gets vaccinated in the near future thank you doctor thank you dr bernstein thanks dr monto i i want to uh express my agreement with everyone else by with over 600 million covet vaccine doses that have been already administered in the u.s we really the overall safety profiles are quite reassuring and i think having a coated vaccine available for this younger population is critically important given that pediatric cases can be have been and may be problematic in the future i also think that there's a huge vaccine safety monitoring system in the united states that's historic and so uh that should be reassuring to many and i do think that there are advances in science in the coven 19 science they they'll continue on for many years not just vaccines but treatments and testing and social distancing masks etc i also think that hybrid immunity will provide more protection against future infections and will be helpful as well even to those who have already experienced cova because i think overall those who are vaccinated tend to do better in all outcomes than those that are unvaccinated and i think that the ultimate aim of covid19 vaccine is to prevent severe disease hospitalization and death more than preventing transmission and infection and i think the message is i want to emphasize what others have said that messaging messaging must be communicated very clearly to the public and i still feel that there are tens of millions of people who are unvaccinated and we must also encourage them to get vaccinated thanks thank you dr levy followed by dr ganz yeah i just wanted to take a moment to acknowledge the public commentary that shows the wide diversity of opinions in the u.s public about this whole vaccine enterprise and i think it becomes important that we continue that tradition of being open to all the public commentary provided it's not hate speech provided it's respectful but to to cast a big tent here and i think what we've heard from a lot of the committee members elites speak for themselves but what i've heard is the emphasis on a choice a choice for families they can partner with their pediatrician make a decision uh if they're in a situation in a community where there's a lot of spread of covid if they have children that may be at higher risk if they have family members who are particularly vulnerable we encourage them if this moves forward to avail themselves of this option so it's a concept of making it available and the ongoing safety surveillance the u.s public should hear that that's a serious enterprise it's not a rubber stamp we've seen entire vaccine programs put on hold for rare cases of thrombosis and i was interviewed in the media saying dr levy isn't it a mistake doesn't it fake public confidence when they stop a program i said to the contrary it should show the public that the safety surveillance works that it's serious and that if we do detect further signals that are concerning something will be done about it so i think this is the right path forward and i'm very honored to be part of this committee thank you thank you dr levy dr ganz followed by dr marasco thank you very much i just wanted to add a voice to the significance of this as a pediatric disease i think as you weigh it in terms of being the fourth and fifth most um risk factor for death is really an important so i think we really do need to not underplay the importance of this as a pediatric disease and therefore prevention is really the way to go and it's also of note it was brought up earlier that there are just all these treatments now that we have for covid but that's not the case for our youngest individuals we actually have very restricted and limited ability to help anyone who's infected and they are actually not that the most efficacious and so i think it's very important the other point i wanted to bring up for the individuals who will be considering this for their families is that infection the immune response that you can get from vaccine versus infection is different you have an infection and you have viral replication and also tissue invasion and damage is different you do get an immune response but getting immune response without that is also should be an option for individuals so that they don't have to suffer from the actual viral disease so i think that's a really important point that hasn't been raised i'm trying not to be repetitive for my colleagues so i know raised some really great points the other aspect i would like to just add to dr levy's point and others on this committee is that we do take the science very seriously and i hope that really has come through to those who maybe are doubting the fact that we're listening we are considering all of the different scientific and i just want to apply the scientific community this is really a breakthrough that has allowed us to move through the pandemic in a way that has allowed less suffering and disease so i'm very glad for this option for people in the scientific community who care for children as well as family thank you thank you thank you dr gaines dr morasco followed by dr lee hi um thank you so i've been impressed as everybody has with the comments by the public they're very important i take them seriously i think we all do it is not escape me or other members of the committee that we've received thousands upon thousands of emails from people on both sides of this issue i think it's really been largely a matter of misinformation or disinformation people thinking that children weren't as susceptible as they were you know earlier in the pandemic i don't think many people understand the increase in infection with omicron but i think it's all about people making the own decisions for themselves and their family dr meisner and everybody else has really said it right it's a matter of choice i just want to make sure the messaging from the cdc and the fda is coordinated in such a way that the health care providers and all the local healthcare providers can also provide that information to help families and parents make this decision so i'm proud to be part of this committee and i agree with the decision that's conveyed dr lee uh yes i just wanted to also add my support for this decision i think um as we heard in the public comment um the lack of the vaccines for these young children has been a gap for many and has really had an impact on the lives so i think this is really really very positive i will say i think it's clear the story isn't over the pandemic has taken some different twists and turns uh and there may be more options for these um children um in the future and i think we will be considering that as well and i'd also like to see i'm very proud to be part of this committee and um and very very i'm pleased with all the clients we've been able to see from the investigators and the companies thank you thank you dr lee that concludes our action on the moderna vaccine we're going to take a break until 3 25 eastern that gives us a little about 15 min about 15 minutes is that right no 10 minutes uh oh 3 25 yeah 15 minutes yes you are right yeah yep a reward for getting done we'll start when we should have been taking the break 15 minutes and then we will repeat what we've just done questions discussion and vote for pfizer all right and with that we will now take our 15-minute break studio studio can you tell us if we're clear [Music] so [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] [Music] my [Music] so [Music] so [Music] [Music] [Music] [Music] do [Music] do [Music] so [Music] bye okay good afternoon and welcome to uh the closing session of the 174th vaccines related biological products advisory committee meeting uh dr anamanto our chair take it away thank you very much we will now repeat the process of questions to both the sponsors and to fda and then discussion and votes and explanation of votes so hands raised for questions for either the sponsor or fda dr marasco followed by dr ganz dr groom uh this uh thank you dr monto dr gruber this is a question for you and um this was really it's a question that was touched on by dr program courtney and office and it really has to do with your three microgram dose so there's a pretty impressive step up in protection from your second or third dose for omnichrome and i had a pretty low dose of mrna and i i heard from your associate that you know you've got good protein production but the question i really am asking is is there a fundamental difference that has occurred with your vaccine in other words because of the low dose that you have given are you getting any different quantitative or qualitative response in terms of for example higher affinity antibodies so when you do your tightering and you get your main geometric tighter you get a number but does that is is that because of higher tighter antibodies more i mean higher titers or more higher affinity to the omicron and those kind of studies can be done quite simply serologically and i'm wondering if you're pursuing that to find out if there's something qualitatively and quantitatively different about the effects you see in your third dose uh thanks for the question i may ask keena swanson to actually come up to provide maybe a little bit more detail but um to this point we haven't actually specifically looked in detail certainly in the pediatric population about the nature of antibody affinity i i come back to the fundamental observation that as best as we can determine the level of neutralizing antibody that we see against omicron seems to reliably predict uh the likelihood that you're going to have protection when that antibody is low regardless of whether it's related to affinity or related to the actual quantity of antibody that's there that has neutralizing potential it predicts the likelihood that you're going to be successful low antibody less efficacy higher antibody higher efficacy and again we've shown uh that antibody that we induce in these young children matches that in older adults after in older children and adults after three doses and provides protection but maybe i can ask dr swanson just to comment on any other sort of work that we're doing related to characterizing antibody hi kena swanson from cyzer viral vaccines and just to add briefly to what dr gruber mentioned i think the key of what we're seeing in the development of the immune response is between the second and the third dose there isn't not only an increase in the neutralizing titer but the activity and binding affinity of those antibodies particularly that you can can notice against omicron and that's been seen in the data in the adults and we're seeing indications that the trend is similar as well in children less than five years of age and there are other publications and pre-prints out there that have done you know a similar analysis in other populations thank you yeah maybe if i can just enlarge on a point because i want to clarify something that was being said this morning that this really interdigitates with and that is that both in the briefing document as well as in the information that the fda shared with you in their slide presentation you've seen kaplan-meier curves and for the two to four-year-olds it's pretty clear uh that whether we're talking about delta or we're talking about omicron even after the second dose you do see you know a spreading of those curves and if you think about it the the amount of delta that we saw is actually dwarfed by the amount of omicron so much of that efficacy that you're seeing even after the second dose is due to um efficacy against omicron for the six months to less than two-year-olds it's less clear about when that efficacy may start to occur but you can see as you go farther out that the curve begins to spread a little bit and the goal really is with the third dose to move everything to the left to maximize the potential that we can have for protection against omicron by giving that third dose thank you dr ganz thank you um and i think i would love to hear some of the vision of what pfizer is going to do we heard quite a bit from moderna about some of the studies that they're going to be doing forthcoming and thank you for providing the ones that we heard about earlier today we don't have to repeat those the ones that i was really um considering is it's not unusual to need a prime prime boost strategy so the three doses here doesn't surprise many people and i think that's all within keeping my question for you particularly because these were developed during a time when there's obviously disease progression variants coming into being what will be your follow-up studies how likely is it that um and probably pretty likely because we're seeing that in adult population but what are you doing to prepare for future doses and are you looking at any other dosing in terms of how much you're giving and the intervals yeah so thanks for that question i we're obviously all looking forward to the end of this month when at the verppak further decisions on the nature of what future vaccines should look like will be informed both by information that we're providing based on our bivalent vaccine experience and our omicron experience in adults we are actually working then on based on the information that comes out of that meeting to best tailor what we would do to investigate young children and as it is no surprise to you dr gantz we have sort of two groups we have to contend with here those that are naive what's going to be best for them moving forward as well as those that we put in good position we hope based on that hopefully today's recommendation from the verpack committee to have them fully primed ready for whatever else we might bring in the future thank you and thanks both to the sponsor and to the fda group we have no more questions from the panel and therefore we will move to discussion of the voting question and could we have the voting question put up so based on totality of evidence do the benefits of the pfizer by antacobit vaccine when administered as a three dose series outweigh its risk for use in infants and children six months through four years of age that is going to be our voting question now discussion we don't want to say how you're voting but you can say whether you support approval so dr office thanks arnold so so um i think that the way that this question is written do the benefits outweigh the risks is um is is something i could support but i do have some concerns about this vaccine i just want to sort of air them it does worry me actually that there was no protection after those two that was surprising i think it was probably surprising to the company the and i feared that they may have underdosed um we were supposed to meet on february 15th to discuss this we didn't i think in part because that those data probably were surprising and with moderna you know you have for example low levels of protective efficacy after those two but you can assume that that probably is predictive of better protection against severe disease i'm not so sure you can predict that with with pfizer's vaccine now on the other hand with the third dose you get the kind of immunobridging data that is is reassuring the neutralizing antibiotics against omicron is reassuring but that's those three so so for people who've gotten that vaccine who've gotten say two doses of that vaccine they have to know they're not protected and and they're gonna have to wait a few months until they are protected and i just wonder whether parents will understand that so um i just i do worry about this because i think it was a surprisingly negative result although the protection protective efficacy that was listed you know with you know 75 percent with a six-month-old to two-year-old and eighty percent for the for the uh for the uh older group it's it's those are based on very small numbers and we use seven seven cases in one instance three cases another it's a little hard to put to uh to feel comfortable about that since the numbers were so low so so i i do support this but i do worry that parents aren't necessarily going to know that after two doses they may not be protected at all and would engage the kind of activity that would put their child at risk so thank you dr offit would you be more comfortable if in the post approval period careful surveillance be given about protection after two doses given the relative relatively small numbers is that something that can't be fixed no i think that's a really good point and and we'll thought as more and more children are vaccinated we'll learn more and it may be that what dr cohn said earlier is true that this may end up being a poor dose vaccine but i do think we should certainly learn as much as we can when it gets out there i think it's safe i think it will it will certainly offer something but i do worry that those those two dose data were surprisingly poor but thank you hey dr chatterjee followed by dr lee thank you dr [ __ ] i was actually going to make a very similar comment to what dr offit did with regard to the two doses not providing sufficient protection um i think with with two vaccines uh that have different dosing regimens it's going to be even more important than ever that the public education the education of providers is done very very carefully so that people understand what the ramifications of the choices that was discussed earlier this afternoon are that we are making choices between two different vaccines that have a little bit different profiles and that's that's going to be important for people to take into consideration having said that uh i would say that i was pleased to see the three dose data um showing um the um that it brings it up to par basically like we see in in older children and adults to the level of protection um recognizing of course that this virus is continually changing and that those numbers are maybe true today and may not be true down the road but with all of those caveats i am in support of the authorization of this vaccine as well making sure again that the education around this is done very very carefully so that people are not misled by what the vaccines actually provide yes and i think we should not underestimate the problems of rolling out various approaches to vaccination which which have different intervals and different doses and the rest this is uh going to be quite challenging uh dr lee followed by dr um cohen thank you so um i share the um uh concerns of the last two speakers about the two dose um data i was also actually quite surprised um i guess my concern is i do recognize that with the three doses there's i have a lot of concern that many of these kids will not get the third dose as we know it's a struggle to get people in for two we've already seen with the boosters for adults lots of people don't take them and so my concern is that you have to get the three doses to really get what you need i'm just concerned that um that some will having said that i will say that i do i am supportive of this bill thank you dr cohen and then dr marks is going to be thank you thank you um i am also very supportive that and agree that the benefits do outweigh the risk of this vaccine just to add to what the previous uh commenters have said i think it is imperative that we you know do post licensure surveillance for effectiveness for both vaccines but in particular not only i'm also concerned about um people comparing the ve estimates or point estimates between these two which i think is a real problem uh given the few number of cases and you know i would really hope in our communications that we not use that 80 effectiveness because my level of confidence in that number i believe the vaccine is effective i do not have any idea what that number will actually end up being and additionally i think it's really important for people to understand not you know that that this was effectiveness after 30 days other vaccines have looked at effectiveness after longer periods of time of follow-up so 30 days after vaccination um you know this could fall off very quickly and we just want to monitor it closely yeah dr cohen you notice the confidence intervals around some of these estimates correct we really can't go with the with with the the point estimates because the confidence intervals for for a lot of them were pretty wide until you grouped together uh dr marks you had some comments i i just sorry i just thought it might be helpful i i i i apologize if i missed this book but i didn't hear the uh the sponsor uh reply to this but it may be helpful um there there does seem to be a lot of mystery around the second dose effectiveness with uh pfizer and it might be helpful for both the public and for the committee if they commented on that two dose effectiveness that's fine i remember they're saying that they the the the kaplan-meier plots did uh separate dr ruber would you would you supplement the information we've got yes so again they're really two lines of evidence we've already spent time showing the slides in terms of the delta response right and for both age groups after a second dose uh we had uh high levels of efficacy both in the six months uh to less than two-year-olds in the uh individuals uh that were two to five we also demonstrated efficacy after delta the real question obviously in an omicron environment is what we're seeing after omicron and uh if my slide pullers can pull it up or people can likely remember it or you may see it in your briefing document again if you looked at the two the less than five-year-olds you see uh separation of the curve yeah let's bring slide one to screen please so keep in mind again that that we only you know we have a total of 10 cases in terms of post three so most of the cases that you're seeing here represent cases after dose two and you can see based on the x axis the number of days and sort of calculate then well if it's 21 days between the first dose and the second dose because this is a kaplan-meier based on the time from the first dose you can see spreading of the curve that starts uh fairly early and then continues to spread uh in the two to four year old so it's not as if there's no efficacy at all the notion is we're building on a level of efficacy that in every other population we regard as insufficient for omicron and the goal here based on what we're showing you with the third dose is to improve upon that efficacy if we then show uh if you put a slide uh slide well let's see yeah um yeah slide yep slide uh one up please so slide one in this case we're talking about the six month to two year olds and it's true that as you walk through most of the period of time here you're not seeing a separation of the curves but given that they're a total of three cases some of that separation at the end may well be due to maturation of immune response and the fact that those children now are beginning to show some evidence of efficacy but the goal with the third dose in this circumstance is to shift that to the left where we essentially can build upon the ability to provide some protection against disease by moving that separation of the curve to the left and keep in mind again as with every other circumstance there's some expectation that protection against severe disease is likely to be higher than what we're seeing against just symptomatic infection hopefully dr marx that helps clarify thank you thank you thanks dr marsh thanks dr gruber and dr ganz it looks like you were going to have the final word in our discussion thank you i just wanted to point out um as a lot of people have pointed out particularly that there's three doses needed here to provide protection but in terms of what the public and parents should expect it's likely that modern is also going to be a food through those schedules so i just wanted to put that into context of what we understand and that doesn't take away from the comments that my colleagues have already provided for the feelings that we have about these different vaccines thank you thank you dr ganz no more hands raised so we move to the vote christina thank you dr monto okay um can you uh please well let's go down to the next slide let's get the right question up okay as you can see before us on the slide here are the members and temporary voting members that will be voting and then dr mata if you could please read the voting questions okay based on the totality of scientific evidence available through the benefits of the pfizer biontech covet 19 vaccine when administered as a three dose series three micrograms each dose outweigh its risks for use in infants and children six months through four years of age okay at this time and go ahead and vote you have two minutes to vote last week this is just trying to get approved okay looks like all the beds are in you can go ahead and close the pole and broadcast the results okay there are 21 total voting members and we have here 21 yes votes this is a unanimous vote and there are zero no votes in zero state and now i will go ahead and read the specific voting responses for the record dr berger yes dr nelson yes dr fuller yes dr levy yes dr monto dr sawyer yes dr offit yes dr reingold yes dr brenstein yes dr mcinnis yes dr wharton yes dr pergam yes dr chatterjee yes dr portnoy yes dr lee yes dr kim yes dr cohn yes dr marasco yes dr meisner yes dr genn's yes dr hildreth yes and that concludes my reading of the specific votes and i will now hand the meeting back over to dr montan thank you and uh before my hand saying oh we have an explanation of votes so dr levy yeah i just wanted to um offer some thoughts here i i'm really uh pleased that we've reached this kind of milestone i i recall our first uh vote uh a year ago or more on the first psizer authorization i was one of the 17 votes in favor i remember those early discussions even then should the 16 and 17 year olds be included at that point that was a controversial topic that was being discussed and here we are now as a committee unanimously recommending uh authorization down to six months of age so uh we've come a long way um you know the warp speed of vaccine initiative uh more or less worked it got a safe and effective vaccines in in record time but i just want to make the point that there's a lot of work to do ahead in vaccinology we have inequities globally in access to the vaccines i'll point out that the majority of the vaccine infrastructure in the world is pediatric and pediatric vaccines achieve higher population penetration for that reason so that's something interesting to contemplate as we think about global inequities and immunization against this pandemic the other point i'll point out and it was evident in the discussion is the number of doses required two three maybe four in immunocompromised individuals maybe five so we're very fortunate to have safe and effective vaccines in record time and yet still we can't all go home now there's a lot of work a lot of research still to be done can we design vaccines that give single shot protection that cover all of the different variants that are pan corona virus vaccines are vaccine adjuvants a potential approach to get a better efficacy with one or two doses instead of needing three four or five doses so this is a public plea to keep supporting around the globe vaccine research so that we can have even better vaccines in the future thank you dr nelson thank you dr monto just a couple of quick comments clearly in favor of the voted question as voted um having options at every age group is important certainly this second vote contributes to that and does contribute to options and choice for families throughout the united states two quick comment slash caveats i do think there is certainly needed data to look specifically at the stratification of both the immune response and the reactogenicity based on the interval between that second and third dose we saw a discordance today with the immunogenicity data generated early but the safety data with the larger groups spread out through that throughout that entire period and with the numbers involved i'm not sure we have the full signal of where that benefit risk ratio is for that third dose to me it probably looks closer to a vaccine like hepatitis b where there is evidence that that third dose actually given later might work but in this case with the gap in efficacy apparently having it closer to that second dose may be advantageous certainly if families are listening air towards that direction and then finally the co-administration issue that has come up over and over today is something that i too have been concerned about going into today's discussion i'm glad to hear the that our sponsors are going to look into the question i will tell you that if we don't get a quick answer to the co-administration question it will serve as a barrier completion of these three dose series for this vaccine and likely the modernity vaccine having to get it in isolation is going to be a great challenge for families and children here in the us thank you dr monto thank you dr nelson dr fuller followed by dr chatterjee yes thank you dr monto i just want to say that the idea of having psizer and moderna it's very good for families and also that we should not forget that the mitigations of masking and these things that work that we know work should not be forgotten even with those who are vaccinated because they're we don't understand the re-infections or the new new infections with new strains so people need to be reminded in the messaging the importance of the things that we do know that works that work such as distancing and and just being careful and using what we know and so i'm very pleased that we have two opportunities to help those with younger families and there's a lot of work still ahead to be done thank you dr chatterjee yes uh thank you destimonto as a pediatrician um today is a red leather day for me uh to be able to vote for authorization of two vaccines uh that will protect uh children um down to six months of age against this deadly virus is a very very important thing and i am also thinking back like uh dr levy to december 10 2020 which is the day that we authorized the very first vaccine for use in people who are 16 years of age and older and i was actually one of the no votes which got me into a lot of trouble but the reasoning behind that we were able to explain that later was the the four of us who voted know that they all had essentially the same reasoning i believe and that was that we had insufficient data in the 16 and 17 year olds we had data only on 150 participants when the ongoing study had 2 000 in it we if we had just waited a little longer we would have had those data um it's it's uh interesting to think back to that time but it's also important to look forward as as dr levy has pointed out there is much work still to be done against this virus and against other infectious disease threats that face our population and so i am just very very grateful to have been part of this effort and i'm i'm delighted that we have been able to recommend authorization for these two vaccines for our very youngest children thank you thank you dr cohen and then dr purgam thanks i just wanted to uh say quickly i'm obviously as a pediatrician super happy that uh we can now vaccinate down to six months of age but really i just want to express my deep gratitude and admiration for the staff at fda who have made this happen because my confidence in this book today is entirely related to the just clearly incredible amount of work that many many staff at fda have put in i can't even the number of people who have presented and put this all together is incredible and i know we have another meeting in two weeks and the work is not done but um i just think taking a moment and thinking um the staff that put all this effort into this i just wanted to do that dr cohen you're stealing my closing remarks but i'm still going to say it when we get to the club dr burgam i just left because amanda always has such great comments and uh always appreciated by other members of the committee i can say that i do think it is important as we have this discussion about the importance of having two vaccines available for children that as the fda thinks about this and cdc in terms of providing vaccine across the country that you know when when the primary vaccine doses were given moderna and pfizer were not adequately distributed in different parts of the country and so i think it's really important that both of these options are available throughout and we're in a different situation with vaccine availability than we were in the past but i think it's going to be really contingent upon both to provide both of these options throughout the us and not have specific locations where one or the other is offered i think it's really important since these are different there are different um caveats that parents may look at when they're offering these to children or making decisions that i think it's critical that they're they're made available across the country dr meisner thank you dr motto one very brief comment uh similar to my comment regarding moderna i think it's the right decision today to make these vaccines available for this age group but i also think it's important that people understand it's a small number of children who have received these vaccines and the safety um is not as well established as it is in adolescents and adults so it's so important to continue to follow the safety profile of these vaccines i again i don't think they should be required for uh any specific situation thank you thank you dr meisner dr marks do you want to make any closing comments and after that i'd like to make some closing comments yeah i know thanks thanks dr monto so um i i'm gonna i think amanda started it uh very nicely but i just wanna just summarize that you know the past two days um we heard um excellent presentations uh from sponsors from fda we heard open public hearing speakers and i think it's it is a bit of a milestone to bring down the age range for these uh vaccines as we work through this i i also think we heard um we have to be aware of the fact that we care tremendously at fda about the safety effectiveness of these vaccines and we will continue to monitor these vaccines as they are deployed i would just remind the public that theirs is a message that captures all adverse events and causality in theirs is not uh it's not established there seems to be a lot of misinformation and i'm i'm saying it right now in real time because i'm watching twitter storms in front of me um about misunderstanding theirs bears anyone can uh is is able to submit an adverse event to theirs we actually require that certain things be submitted to theirs uh and so it can from casual inspection of theirs look like there are things that are associated with the vaccines but until one sorts through that uh one does not know what is truly associated with the vaccines and indeed we have experts that spend a lot of time and that pride themselves they work day and night to ensure that they understand the safety profile of these vaccines that has been done and will continue to be done diligently and as we have findings as we did with myocarditis um thrombosis thrombocytopenia syndrome giambare syndrome for uh rare adverse events we will make sure the public knows about them so i just want to say that i want to just remind people of that and just take a final moment to thank the committee members for an incredible amount of time and thank our fda staff who have really worked beyond anything that could ever have been expected of them from the advisory committee staff to those helping to run today's meeting technically to those reviewers and management in the office of vaccines and the office of biostatistics and pharmacovigilance and biologic quality who have relentlessly worked on this very grateful for all their work thank you and thank you dr mondo for for sharing this meeting i'll turn it back over to you and i wanted to thank you dr marks and your staff for an enormous amount of work that's gone into this i was glad to hear our committee members remember back to december 10th 2020 when we first approved a vaccine for sars kobe 2 virus and the fact that there were negative votes and we've now a year and a half later almost to the day uh approved a vaccine for down to age six months of age so essentially all of the american population can now choose or be chosen to get vaccine and we had some negative votes there and i remember that we didn't even have time because we were running over and all sorts of things going on because of the uh pressure to get vaccines approved at that point and we didn't have the time to have individuals like dr chatterjee explain their vote which wasn't against the vaccine but the fact that we didn't have sufficient data what's happened since that time is that we have had observational studies which have guided us in terms of the parade of variants that we've had since that time the need for booster doses and now a year and a half later we've got pediatric vaccines approved down to age six months why a year and a half because of a lot of things that have happened over that time it has not been easy and to say that there are have been delays unnecessary delays is not representing the true situation which involved not working with adults but with a vulnerable younger population for whom special care is necessary so in closing i would like to let the public know how hard dr marx and the entire staff at fda have worked to reach this milestone when we organize these meetings emails come in at 11 o'clock at night over the weekend people are working overtime to get the public availability of these nearly miraculous vaccines i work in flu where if we have 50 60 effectiveness that's pretty good and here we have vaccines which are highly effective in preventing severe disease so i'm very delighted to have had the privilege of sharing these sessions in getting us these very critically important vaccines i just wish everybody would realize how well they work in preventing severe disease i will would like to close this meeting and hand this over for the official closing to dr atreya and thank you dr atreya we've got and i hope you get some rest so you don't have to send send me emails at 11 o'clock at night when i can't read things through my regular email system thank you no problem thank you all with that uh with those closing content i really thank the whole committee and the staff and involved in working really hard and then uh making this meeting successful i greatly appreciate and so with that i officially attend the meeting for today thank you all and namaste all right anyone's that uh this meeting has been officially adjourned uh any questions or comments please send them to our email address and have a great day studio please end the meeting you
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