October 2020 ACIP Meeting – Cholera Vaccines & Zoster Vaccine

>> Good morning, everyone This is Jose Romero We are ready to start the second day of the October ACIP meeting I hope you’ve all slept well We’ve had some power issues here in Atlanta So I’m going to begin by gaveling, the meeting to order Sorry, no gavel, just my knuckles So we’re going to take an abbreviated roll call this morning, just the ACIP members I’m going to call your names and please indicate whether you’re present No need to give affiliations or conflicts of interest So I will begin So Dr. Robert Atmar >> Present >> Dr. Kevin Ault Okay. I’ll come back to that Miss Lynn Bahta I’ll come back Dr. Beth Bell >> Present >> Dr. Hank Bernstein Okay, I’ll come back Dr. Sharon Frey >> Present >> Dr. Paul Hunter >> Present >> Dr. Grace Lee >> Present >> Miss Veronica McNally >> Present >> Dr. Katherine Poeling I’ll come back Dr. Pablo Sanchez >> Present >> Thank you, Dr Peter Szilagyi >> Present >> Dr. Keipp Talbot >> Present >> Starting from the top Dr. Kevin Ault Miss Lynn Bahta >> Kevin’s here He’s unmuted, but he must be on auto mute >> Dr. Hank Bernstein Dr. Katherine Poeling Oh, I called you Never mind Sorry. Okay Lynn are you on? All right, we’ll come back and fill in the gaps here Let’s do the agency updates first So let me begin with Dr. Messonier >> Great, thank you You’ll be hearing more about CDC’s response to the COVID-19 pandemic tomorrow, but I wanted to share a few notes about the breadth of CDC’s work on this response CDC has been actively responding to the COVID-19 pandemic for nearly 300 days In fact, today is Day 298 since NCRD activated in January 7,400 CDC staff have participated in the response, representing 3.5 million hours logged in responding to this event And given that CDC step is about 10,000 people total, you’ll see that the vast majority of CDC staff have been engaged directly in the response And I expect the rest have been engaged in filling behind those who have been deployed Tomorrow you’ll hear about our epidemiology and vaccine related activities But CDC staff remain committed to responding more broadly, including activities to support data and analytics, laboratory diagnostics and testing, global migration including traveler’s health, contact tracing, state and tribal support, health systems and mitigation for schools, work sites and food systems I next want to turn to talk about routine vaccine coverage, something that we’re not going to be talking about at this meeting, but I know something that the ACIP members care a lot about We recently published results from the 2019 NIS teen and NIS child surveys Both reports identify strong immunization coverage, but also areas where we can do more to reduce disparities The results of the 2019 NIS child found that for example, only 1.2% of children had received no vaccinations by age 24 months But we continued to see disparities in coverage by race, ethnicity, poverty, and Metropolitan statistical area NAS Child was released in August Adolescent vaccination generally was showing improvement However, we all realize that the impact of the COVID pandemic

on childhood immunization is actually pretty extreme And despite lots of efforts, we’re still seeing lagging child and adolescent vaccination coverage I think the gap in measles vaccine is telling We’re apparently somewhere around 1.5 million doses of measles vaccine behind where we should be this year And that means a large number of children unprotected against routine childhood diseases And so this is really a call to action to everyone at this meeting that we need to ensure that children are caught up on their vaccinations You know, if they fall behind and they continue to fall behind, then that puts us at risk for vaccine preventable disease epidemics, as well as for HPV, for example, and the cancers related to it So I hope that you will join us in really trying to emphasize the importance of getting people back to get caught up on these visits You heard about our flu vaccine activities yesterday, but I want to emphasize that we’re also working to improve flu coverage in this season, and to address disparities in flu vaccination and flu outcomes Our estimates from last season show that vaccine coverage increased slightly among adults from the previous season, yet racial, ethnic disparities in flu vaccination coverage persist And in an average year, more than half of US adults remain unprotected against flu A recent analysis of flu hospitalization rates by race and ethnicity during 10 flu seasons showed that non-Hispanic black persons had the highest flu hospitalization rates, followed by non-Hispanic American Indian or Alaskan natives, and then Hispanic or Latino persons compared to non-Hispanic whites Among other activities to address these ongoing disparities, CDC, the AMA and the Ad Council launched a collaborative campaign called No Time for Flu to increase awareness about the importance of flu vaccination, especially among African American and Hispanic audiences This year, we’re seeing a large upsurge in demand for flu vaccine compared to other years And that’s great news But what we need is help sustaining that increase throughout the entire sort of last quarter of this year You know, we optimally want everyone vaccinated in October, but we need to keep passing the message along that if folks didn’t get their vaccine in October, November and December, it’s still not too late to get vaccinated Acute flaccid myelitis is something we’ve talked about, even though it’s not vaccine preventable It’s uncertain how the COVID-19 pandemic and recommended social distancing will affect enterovirus circulation in the US, but we were prepared for a surge in cases Considering that we thought 2020 would follow the pattern of national increases in AFM every two years And in fact, we’re not seeing that this year So we are still on high alert for AFM But we will need to continue to determine the impact of social distancing on that as well as on other respiratory viral diseases Finally, you know, in a time where there is so much bad news, I want to end on a happy note, which is that World Polio Day was celebrated last week, October 24 As an opportunity to highlight global efforts towards a polio-free world and honor the tireless contributions of those on the frontlines in the fight to eradicate polio from every corner in the globe This year, there is additional reason to celebrate on October 25th, 2020, the Africa region was officially certified as wild poliovirus free, with the African region certification, five of the six WHO regions representing over 90% of the world’s population are now free of wild poliovirus Thanks for the time, I’ll turn it back >> Thank you very much for that update Next, Centers for Medicaid and Medicare Services please update >> Thank you This is Mary Beth Hance from the Centers for Medicare Medicaid services I have a few updates Yesterday CMS issued the fourth COVID-19 interim final rule with comment period that addresses coverage of COVID-19 vaccines in Medicare, Medicaid, and private health plans In addition, CMS issued three COVID-19 toolkits aimed at state Medicaid agencies, providers who will administer covered vaccine and health insurance plans All of these materials are available on that on cms.gov Regarding flu, CMS has coordinated with CDC

on the release of their flu campaign materials Flu materials include videos, fliers, and drop in articles all in both Spanish and English, and they’re all available on medicare.gov In addition, consumers who subscribe for email updates from Medicare have received a specific email about the importance of flu vaccine Postcards have also been sent to those who are dually eligible for Medicare and Medicaid And the CMS Office of Minority Health has also included flu vaccine information on their website Specific to pediatric vaccines, CMS has repeatedly emphasized the importance of routine immunizations to states and other partners In both June and July, CDC ISD staff joined CMS calls with both state Medicaid and Children’s Health Insurance Program staff and emphasize the need for catch up vaccines CMS has a Connecting Kids to Coverage Campaign and materials specific to vaccines are available on that website Thank you Thank you very much for that update Food and Drug Administration update, please >> Good morning, this is Doran Fink for FDA Earlier this month, FDA published guidance on data to support emergency use authorization last week by an open session of the vaccines and related aid for general discussion Considerations for the development, licensure and/or emergency use authorization of COVID-19 preventive vaccines I will be discussing the VRPC meeting in more detail during the COVID-19 vaccine session tomorrow Thank you >> Thank you very much for your update Next, Health Resources and Services Administration update, please >> Good morning This is Mary Rubin Thank you for allowing me to provide updates on the Division of Injury Compensation Program activities The National Vaccine Injury Compensation Program, the ICB continues to process an increased number of claims In fiscal year 2020 petitioners filed 1,191 claims with the program $186.8 million was awarded to petitioners, and $31 million was awarded to pay attorneys’ fees and costs In addition, at the end of fiscal year 2020 HERSA had a backlog of 966 Vaccine Injury claims awaiting for review As of October 1, 2020, the Countermeasures Injury Compensation Program, CICP, determined that 39 claims were eligible for compensation totaling $6 million The CICP also published a notice of proposed rulemaking for the smallpox Countermeasures Injury Compensation for injury table, and this was published in the Federal Register on 10/15/2020 The comment period ends on December 14, 2020 That’ ends my update Thank you >> Thank you very much Indian health services, please >> Good morning This is Tom Weiser for Indian Health Service We have several updates on COVID planning So IHS has established a COVID vaccine taskforce to develop agency-wide plan for vaccine allocation and distribution to IHS, tribal and Urban Health Facilities who choose to receive their vaccine from HIS IHS vaccine task force teams are focused on distribution prioritization, administration, communication, data management and safety Regarding VAERS, the vaccine adverse event monitoring through VAERS, and active internal reporting systems that are based on current monitoring for COVID-19 treatments have been developed The IHS appreciates the development of a new element to VAERS this year For the first time, we’re recording specifically to HIS IHS Pharmacy and Therapeutics Committee will be providing outreach to IHS tribal and urban Indian Health Program sites to ensure they’re familiar with reporting systems and understand the importance of close safety monitoring Regarding COVID-19 in general, while data published in the NMWR in August described at least a threefold higher incidence of COVID-19 for American Indians and Alaska Natives compared to non-Hispanic whites, data on underlying conditions, hospitalizations and mortality is insufficient at this time

to fully assess the severity of the COVID-19 pandemic in American Indian and Alaska Native communities Despite this, IHS greatly appreciates the continued assistance provided by the CDC tribal support unit as mentioned previously Regarding influenza and reporting the IHS is monitoring influenza like illness from 2020-2021 influenza season It has also created a developmental COVID like illness surveillance report Influenza vaccination activities demonstrate higher uptake of influenza vaccine early in the season compared to previous years As of October 10th, 2020, 11.6% have received at least one dose of seasonal influenza vaccine in patients six months and older compared to 8.5% at the same time last year And finally regarding routine and catch up immunizations, during COVID-19, reported American Indian/Alaskan Native childhood immunization coverage has decreased IHS has engaged in various initiatives to promote routine and catch up immunizations during COVID-19 This has included hosting webinars, sharing CDC and HHS communication and education materials, provider resources and toolkits And again, IHS appreciates the ongoing support of CDC in these efforts as well That concludes my report Thank you >> Thank you very much National Institutes of Health update, please >> Yeah, yeah Good morning This is John Beigel Reporting for the NIH There are just a few updates I think might be of interest to the committee Number one, there was reports in New England Journal of Medicine about a month ago for the NYAD phase one study at the mRNA 1273, the Moderna vaccine for COVID-19 This was a follow-on to a prior report But this is important because this actually detailed the experience in older adults defined in this study as age 56 years and older And it showed that the vaccine is well tolerated and generated a very robust immune response And that set the stage for having that population in the larger pivotal studies NYAD continues to support the large pivotal phase three studies through its COVID-19 provision network or what we call CovPN About a week ago, Moderna completed the full enrollment into the mRNA 1273 phase three study And a fourth vaccine study has actually been started This one is the Johnson — the Johnson which is the J&J product So this gives us for large pivotal studies currently ongoing to try to get an effective vaccine for this, for COVID-19 And then shifting just to briefly to AFM, NYAD awarded a contract to begin development of a vaccine for enterovirus D68 which is the — as everyone knows — the respiratory virus that causes the acute flaccid myelitis So this is just beginning development, but we think is critically needed in order to prevent this devastating disease And those are the updates from the NIH Thank you >> Thank you very much Office of Infectious Diseases and HIV/AIDS Policy, please >> To help support the flu vaccination efforts by CDC and other agencies, we created an online toolkit that provides materials designed to encourage everyone to get their flu vaccine by Halloween The Boo to the Flu toolkit includes social media graphics, posts and others to help drive the CDC messaging about getting the flu vaccine by the end of October Partners can use any of these materials that they would like by visiting vaccines.gov and all OIDP will continue to promote vaccination throughout the flu season OIDP has continued to work on an updated National Vaccine plan with support from the interagency vaccine work group whose members include the federal agencies represented in ACIP plus others But the National Vaccine plan is scheduled to undergo an abbreviated round of public comment period in November And we’re planning on releasing the report, the plan by the end of 2020 or in early 2021

The National Vaccine Advisory Committee, NVAC, met on October 16th and reviewed a draft report containing responses to questions on COVID-19 vaccination posed by Admiral Brett Giroir, the Assistant Secretary for Health The committee will meet again in December to continue to work on this and will potentially get that final report The NVAC website will be updated once the meeting date has been finalized So this concludes the updates from OIDP Thank you >> Thank you very much Thank you all for your updates So what we will do now is proceed to the cholera vaccine presentation And that will be followed by the vote that was delayed from yesterday And then we will resume the normally noted schedule on your handouts So if I could ask Dr. Pablo Sanchez to give the workgroup introduction Dr. Sanchez >> Thank you, Jose So I want to introduce the cholera vaccine workgroup I’ll be the chair of public lectures Next slide The workgroup members consist of as you see here, other ACIP members, ex officio members, liaison representatives, consultants And I really want to give a strong, you know, show of support to our CDC liaison Jen Collins has been absolutely wonderful in forming this group Others, next slide Other CDC contributors are listed here Next slide So back on purpose Well, in 2017 ACIP recommended the cholera vaccine for adult travelers aged 18 to 64 years from the United States to an area of active cholera transmission So this work group now will review more recent data in pediatrics to inform whether ACIP should recommend cholera vaccine for those travelers aged two to 17 years Next slide Next slide So the policy topic that we will consider is should ACIP cholera vaccine recommendations be expanded to include children and adolescents aged two to 17 years? Next So we are developing evidence based recommendations using the grade approach and then eventually update MMR on the recommendations of the ACIP Next slide So thank you for that I do want to mention one other aspect is that the company Emergent Solutions that makes the cholera vaccine naturally make the decision to temporarily discontinue the product distribution as of December 17th, 2020, due to significant reductions in demand And I’m welcome to take any questions but representatives from the company are on the call here as well And, you know, they would like to say some words about that Thank you >> Thanks This is Dr. Mark Schneider I’m happy to speak briefly on behalf of Emergent if that’s okay with the committee >> Please go forward >> Thank you So good morning I’m Dr. Mark Schneider and I’m here actually representing medical affairs for the vaccines division of Emergent Biosolutions I’m also joined by my colleague Dr. Stephanie Campbell Thank you both for the question and the invite here and the opportunity to speak Emergent has made a very difficult decision to temporarily discontinue distribution of Vaxchora and Vivotif due to market reduction and demand Emergent continuously assesses travel data from a wide range of sources to include but not limited to government institutions, external research firms and industry experts that all point to a protracted recovery period for international travel due to the COVID-19 pandemic Pending further notification, the last shipment date for Vaxchora and Vivotif will be December 17th of 2020 Customers can continue through that date

All product being distributed today through December 17th will have an expiration of January of 2021 for Vivotif, and June of 2021 for Vaxchora With that said, please understand that Emergent remains fully committed to addressing the needs of public health and travel medicine as we seek to properly position ourselves for the anticipated return of global travel, and our products to market in the near future >> Excuse me — excuse us >> Sure >> Excuse us We apologize, we did not realize that you were on the agenda and this would not be the appropriate time on the agenda to speak We need to only have our agenda — we need to follow our agenda and not have outside companies speak unless they were previously approved So can you please hold on your comments, and we will try to find some time to add you to the agenda at a later time? Thank you >> Certainly Thank you >> Thank you Sorry for the confusion >> So I’m sorry about that But I did want to remind people, that the Vaxchora is the only licensed and approved cholera vaccine Our workgroup will be looking at the other pediatric indication or recommendation, I should say >> Thank you Thank you for your comments All right Let me go back and take the roll of the individuals that were missing initially Dr. Ault indicated that he was having some audio problems Kevin — Dr. Ault, have you resolve your problems? >> I hope so I’m here and I have no conflicts >> That thank you very much So just say present, no need to state comments — sorry conflicts at this time Miss Lynn Bahta >> I am here Sorry about that My computer died right at the beginning >> No apologies necessary Dr. Bernstein >> Good morning, sorry And I had technical difficulties as well I am present >> No apologies necessary Lastly, Dr. Poeling >> Present Thank you >> Thank you all So we have a full attendance of the members And so we will now proceed to the vote from yesterday, which is the immunization schedule Dr. Friedman, will you take over please? >> Okay, so before the vote, I just wanted to review what we discussed and what the issues were that were pending, and just present a few quick slides before the vote So the first issue that came up was the wording under the child schedule, the notes for the tetanus, diphtheria and pertussis or TDAP vaccination There was a comment about combining the second and third bullet because we wanted to emphasize that TDAP may be administered regardless of the interval since the last tetanus and diphtheria containing vaccine And it does apply to pregnancy So there was a request to combine the two bullets However, it also does apply to some other situations For example, if a child inadvertently was given TDAP between seven and nine years of age, it would still be recommended to get a TDAP booster at age 11 to 12 years of age And so we wanted to go ahead and keep those bullets separate because it does apply to more than just pregnancy And if I can get the slides to advance, there we go I wanted to show table one of the child schedule just to show in the highlighted cell here that we have used the asterisk alone without any text overlay and that is in preparation for the table three comment that we had yesterday If I can get the slides to advance There we go We have taken the recommendation for measles, mumps, rubella, varicella and human papilloma virus asterisk and removed the language that said not recommended

And then the key for the red will indicate that the asterisk indicates vaccinate after pregnancy We will be adding a line space between the word administered and the asterisk vaccine after pregnancy So it stands out more Then on the adult schedule for table two, we decided to leave not recommended with an asterisk for VAR, MMR and HPV Because the adult schedule has traditionally used more text overlay, so we will leave that for recombinant zoster vaccine For the pregnancy column, we changed it from a red with the not recommended asterisk text overlay to gray which means there is no recommendation, which is exactly what is the published recommendation And so that would make that there is no recommendation for pregnancy, immunocompromised and HIV infection because that is the guidance right now So those were the changes that were requested or the discussions that we had Those are our proposals and we are now ready for the vote, and the vote is to recommend the proposed edits to both the 2021 adult and child and adolescent immunization schedules >> Thank you for that presentation So any questions or comments from the voting members? From the liaisons, any questions or comments? Okay, then I need a motion from the voting members to accept the wording as stated, recommend the proposed edits to the 2021 adult and child adolescent immunization schedules as presented Do I have a motion? Dr. Atmar, I see your hand went up first Do you make a motion? Dr. Atmar, are you still having audio problems? Let me go then to Dr. Poeling Dr. Poeling, do you want to motion? >> This is Dr. Atmar I so move >> Okay, thank you, Dr. Atmar I need a second please >> I will second >> Thank you very much Thank you, Dr. Poeling Okay, so open for discussion All right So I’m going to read the list of names and please indicate whether you are in favor of the recommendation or against So alphabetically Dr. Atmar, please I will come back to you, Dr. Atmar Dr. Ault? >> In favor >> Thank you Miss Bahta I will come back to Miss Bahta >> Thank you members We are enabling your unmute buttons Please try again >> So I’m going to run through the list of names and please just indicate if you are able to unmute Dr. Atmar You are? >> Yes. Atmar, yes Thank you, sir Dr. Ault? >> Yes >> Miss Bahta? >> Yes >> Dr. Bell? >> Yes >> Dr. Bernstein? Yes >> Dr. Frey? Dr. Frey? Sharon may still be having problems Dr. Hunter? >> Hunter, yes >> Dr. Lee, can you unmute? >> Yes >> Okay >> Lee, yes >> Okay. Miss McNally >> Yes,

>> Dr. Poeling >> Yes >> Dr. Sanchez? >> Yes >> Dr. Szilagyi? >> Yes >> Dr. Talbot? >> Yes >> Okay. Let me go back to Dr. Frey Dr. Frey, are you able to unmute? >> Yes >> Okay. So now I’m going to try to take the vote We’ll go forward here very quickly So indicate whether you are in favor Yes. Or against the recommendation No. Doctor Atmar >> Atmar, yes >> Dr. Ault? >> Ault, yes >> Miss Bahta? >> Yes >> Dr. Bell? >> Bell, yes >> Dr. Bernstein >> Bernstein, yes >> Dr. Frey? >> Frey, yes >> Dr. Hunter? >> Hunter, yes >> Dr. Lee? >> Lee, yes >> Miss McNally >> McNally, yes >> Dr. Poeling >> Poeling, yes >> Dr. Sanchez >> Sanchez, yes >> Dr. Szilagyi? >> Szilagyi, yes >> Dr. Talbot? >> Talbot, yes >> And Romero, yes So the motion passes unanimously We’ll adopt the schedule as was indicated Thank you very much, and forgive the technical difficulties So we’re now going to move on to the zoster vaccine And we’ll have an introduction by Dr. Lee You can all mute yourselves at this moment, please >> Thanks very much So this is Grace Lee I am the chair of the herpes zoster workgroup If you could move to the next slide, please I first wanted to acknowledge our 2020 herpes zoster workgroup members, including Lynn Bahta, who is an ACIP member, our ex officio and liaison representatives and our consultants who are providing important expertise on key issues related to the use of recombinant zoster vaccine And especially would like to thank Dr. Tara Anderson for her leadership of this group Next slide Can I have the — thank you As a reminder, the ACIP made the following recommendations in October of 2017 First, that recombinant zoster vaccine, which we’ll call RZV going forward, is recommended for the prevention of herpes zoster and related complications for immunocompetent adults aged 50 and older Second, that RZV is recommended for the prevention of herpes zoster and related complications for immunocompetent adults who previously received zoster vaccine live or ZVL And number three, that RZV is preferred over ZVL for the prevention of herpes zoster and related complications The evidence and rationale for the decision in October 2017 can be found in Dr. Dualing’s publication in MMWR listed here along with the grade tables on the ACIP website Next slide Since that time, there have been a few notable updates First for ZVL, effective July 1st, 2020, Zostavax will no longer be sold in the United States The remaining product will expire by November 18th, 2020 And second, that RZV Shingrix, 33 million doses have been distributed from launch through the second quarter of 2020 Shingrix inventory is currently available to meet the demand across all distribution channels And third, that the European Commission or the EMA approved an expanded indication on August 25th, 2020 So Shingrix is now approved in the European Union for prevention of herpes zoster and post-herpetic neuralgia in adults 50 and older and adults 18 years of age or older who are at increased risk of herpes zoster Next slide One more update Oh, actually, can we go back one slide? I apologize I did want to update just verbally that a supplemental biologics license application or BLA was submitted to the US FDA on September 24th, 2020 to expand the indication of Shingrix to include the prevention of herpes zoster in adults 18 years

of age or older who are increased risk for zoster due to immunodeficiency or immunosuppression caused by either disease or therapy So following the European Commission’s approval Next slide Another important update to highlight in the context of the COVID-19 pandemic, in adults 65 and older in the US, we have been reviewing weekly uptake data for RZV between January and July 2019, shown by the blue bars That was steady and increasing over time However, during the same time period between January and July of 2020, shown in the orange bars here, we saw a steep decline in the number of doses administered after the national emergency was declared on March 13th And this is concerning because we have a cohort of older adults who may not be protected against herpes zoster and its complications These numbers are now rising, and we anticipate that we’ll continue to track how the pandemic is affecting health care utilization and vaccination rates in the US But I also wanted to just take a moment and echo Dr. Messonier’s comments from earlier today, that we hope our immunization partners will continue to support vaccination efforts for all age groups during the pandemic So it’s affecting children, adolescents and adults throughout our healthcare systems Next slide In June 2019, the ACIP workgroup presented a summary of RZV post licensure safety monitoring updates from three federal safety surveillance systems: VAERS, VSD and CMS or Medicare, as well as a summary of the herpes zoster workgroup interpretation of these findings The workgroup has met 14 more times since that time to review the data on RZV post licensure safety and uptake monitoring, RZV efficacy and immunogenicity in both immuno competent and immunocompromised adults And we have developed the Pico question for use of RZV in immunocompromised adults in order to develop the evidence to recommendations framework needed to guide a recommendation Next slide So today, we’d like to focus on RZV safety monitoring updates and next steps The presentations today will include an update on post licensure safety monitoring of RZV and in VAERS, a VSD update on post licensure safety monitoring of RZV, data on the risk of Guillian-Barre syndrome following herpes zoster infection, and a summary and planned risk benefit analysis regarding the use of RZV in immunocompetent adults And with that, I’d like to hand it over to my colleagues So our next presentation — thank you, Dr. Lee So our next presentation will be by Dr. John Sue on the update on post licensure safety monitoring of recombinant zoster vaccine in the Vaccine Adverse Event Reporting System, and then will be followed by Dr. Nelson We will hold questions until after the presentation by Dr. Nelson Dr. Sue, please >> Hi. Can you hear me okay? >> Yes, we can >> Sorry, I’m not hearing at all >> Thank you very much for letting us know, Dr. Bell We’re working on the difficulty here Just a second Dr. Sue — >> Thank you for having me this morning Yes, please Excellent Next slide, please Okay. Okay And the second slide has the standard disclaimer Next slide Thank you So just a little brief reminder that VAERS is a passive surveillance system comanaged by CDC and FDA Next slide, please And I do apologize I’m calling in over a cell phone due to power outage issues, so the data may be a little slower on my end So as mentioned, VAERS is a vaccine reporting system

So if people wish to file a report with VAERS, they can go to vaers.hhs.gov and access the website that you see on this slide and fill out an electronic form online, with the different data elements collected, a few of which are shown on the slide here And it’s a fillable PDF, where people can fill that data in offline and then submit at their leisure Next slide, please So as mentioned, VAERS is a past reporting system and so we accept reports from all reporters And, as a result, we don’t really accept — we don’t pass judgment on causality or the clinical severity of the event I’m seeing some texts that indicate that people are not hearing me Okay, should I continue talking? >> Go ahead So let me explain for those listening in So the Atlanta area had some very severe storms last night with trees down and power outages And this is probably affecting communications We’re having problems with communications here at the control center So we will continue to work through this as we can Please bear with us It is beyond our control Thank you very much Please go ahead, Dr. Sue >> Jose, this is Tom [inaudible] Can you hear me okay? >> I can, Tom >> Do you want me just to take over? >> Yeah >> I can attempt to do this I should be okay >> Thank you >> I’m in my office so I can do this >> Thank you, Tom John, we appreciate your effort to get this done Let’s give it over to Tom I’m getting a nod from Dr. Messonier And from Amanda Cohn and Jessica So go ahead Tom, thank you very much for volunteering >> Sure. So as Dr Sue was saying, VAERS passive surveillance system that’s comanaged by CDC and FDA The strengths of VAERS are that it can rapidly detect safety signals and can detect rare adverse events It’s subject to the limitations of passive surveillance systems in general The main limitation is generally we cannot assess causality from VAERS data alone VAERS accepts all reports from all reporters It does not judge causality or clinical severity It’s an early warning system So as a signal detection or hypothesis generating system, and requires if we do identify signals that need additional follow up — we need to move to more robust systems Next slide So this is some data from an MMWR on those published in 2/19, which was the initial published data following the rollout of Shingrix And if you see from this data, most reports were nonserious, 97% And that’s consistent with what we see for other vaccines administered in this age group, namely flu vaccine The most common adverse events were systemic symptoms like fever, chills, headache, and also injection site reactions Next slide So what we’ve done is we’ve gone and updated that analysis with data running through October of 2020 And we’re really not — although there are more reports, as you will see, we’re really not seeing any appreciable changes in the safety profile of Shingrix vaccine as more individuals have been vaccinated We still have the breakdown of serious versus nonserious at about 97% which is consistent with the initial data And I will mention RZV is primarily given alone Over 90% of these doses are administered without other concomitant vaccines Next slide And again, this is the more detailed breakdown of the specific adverse events as coded by MEDRA And you can see they look very similar to the initial data, mainly systemic reactions like fever, headache, fatigue, and chills and also injection site reactions as well Next slide So your recall that there was a signal

in in VSD rapid cycle analysis fairly early on for Guillian-Barre syndrome And there was also a finding of an association when we went to the CMS data with our partners in FDA And we’re presenting the slide just to give you an update on what we’re seeing as far as VAERS reports for GBS So during the period there, October 2017 to April 2019, there were 46 reports of GBS, 3 met Brighton criteria When we move to the next period, May 29, through October 2020, we had 44 additional reports of GDS 27 met the Brighton criteria where one is the highest level of certainty, 16 were physician — I’m sorry 16 of those met Brighton level and 11 were physician diagnosed And 93% of these developed symptoms within 42 days of vaccination, which is the risk window we use for monitoring Next slide And I will mention just before I get to the data mining, that following me will be a presentation on the VSD surveillance And data mining, we did have one data mining finding That was product administered to a patient of inappropriate age, which is a medication error So a data mining finding but not an adverse event following — not an adverse health event following immunization Next slide So in summary, as of October 2020, the RZV post licensure safety monitoring findings in VAERS are generally consistent with the safety profile observed in the pre licensure clinical trials Most reported systemic adverse events or injection site reactions, serious adverse events were rare, 2.6% of reports And that’s similar to other vaccines administered in this age group The number and the composition of reports for GBS were comparable when comparing to the last update And there were no disproportionality findings other than that medication error of inappropriate age Next slide So I’d like to thank the following individuals And are we moving on to the next presentation or taking questions now? >> We’re going to wait until at the end of the next presentation Thanks, Tom >> Okay >> Dr. Nelson, do you have a good enough link to give your presentation? >> I believe so Can you hear me? >> We can It sounds pretty clear And let me just commend John, because previously — before you begin — because I understand that he was in his garage with a generator trying to make his call So thank you very much for attempting to do that And please go ahead, Dr. Nelson >> Thank you Thanks for the opportunity to present today I’ll be presenting the vaccine safety data link update on safety monitoring of RZV Next slide I want to acknowledge a broad team that helped with this work It’s led out of KP Washington, but in collaboration with many colleagues at CDC and other VSD sites Next slide So as a reminder, the VSD is a public health and research collaboration that was established in 1990 between CDC and eight integrated healthcare organizations in the US It captures and curates medical and demographic data currently on about 12 million people or about 3.7% of the US population Next slide The VSD captures and links electronically available data elements as well as conducts manual review of medical charts, since these data are not collected for research purposes The key domains are shown here, which include immunizations, potential adverse events that are defined primarily using ICD 9 or 10 codes that occur in outpatient emergency department or inpatient settings Next slide So the results that I’ll share today for RZV were obtained using VSDs targeted surveillance methodology that uses data like these from across the VSD This methodology is also referred to as rapid cycle analysis It was established in 2006 for conducting near real time vaccine safety monitoring And like a traditional epidemiologic study that you may be familiar with we prespecify our primary vaccine

exposure, in this case RZV, and compared our populations that we think will work well We identify and prespecify adverse event outcome targets of interest, typically about 5 to 10, as well as potential factors that may confound the relationship between exposure and outcome However, unlike a traditional epidemiologic study, instead of waiting for a typical two-year of study to say complete and do a single analysis at the end of that period, in rapid surveillance, we routinely and cumulatively update the study data over time, potentially weekly or monthly And then we conduct repeated interim analyses over time to compare risks between groups Statistically significant findings are deemed to be preliminary signals that are fully investigated with numerous follow activities, including chart validation, often to confirm true incident cases Next slide So here are the design details for the RZV surveillance activity We aim to sequentially monitor RZV among adults 50 years of age and older during the uptake period initially for RZV which in the VSD was January 2018 And we followed through December 2019 Our primary analysis involved comparing RZV recipients with those who received a Zostavax historically, in the prior two to five years Secondary analysis involved age comparable concurrent competitors, so those who had either a well visit or received another vaccine like pneumonia or TDAP during the RZV uptake period We measured a number of baseline covariates, including dose, receipt of concomitant vaccines, prior receipt of ZVL, healthcare utilization measures, as well as a number of medical conditions In terms of the sequential testing plan, the interim analysis involved conducting our first analysis after six months of uptake in June of 2018, and then conducting 18 more monthly analysis subsequently Next slide So we designated two sets of prespecified health outcomes of interest listed in these two bullets We conducted formal sequential analyses for 10 high-priority outcomes occurring instantly in the 42 days post vaccination They’re listed here Anaphylaxis is one outcome where the outcome window is much shorter, zero to one days post vaccination We also conducted an exploratory analysis for a number of other outcomes that are listed in the second bullet, either one to 42 days post vaccination for outcomes like gout and pneumonia, or one to seven days for systemic and local reactions Next slide So here’s a plot of RZV uptake over time in our study At the time of our final monthly analysis, which is indicated by the vertical dashed line, we’d observed almost 650,000 doses And as you can see, we had steady uptake during the approximately two-year surveillance period Next slide So here are the primary sequential results for our 10 primary outcomes The outcomes of interest are shown down the rows and in the table across the columns, we show the observed number of events among RZV recipients, the number of events expected based on historical rates in ZVL recipients The observed rate per hundred thousand people, doses, the relative risk and then whether or not a preliminary signal was identified So as you can see here, for most outcomes, there was no preliminary signal observed and the estimated relative risk was less than one We did detect two preliminary signals, one for Bell’s palsy at the fifth analysis, when there were 36 observed events as compared to 24 that were expected That led to an estimated relative risk of 1.5 But this effect has attenuated over time with twice as much data and the relative risk currently shown here, as you can see, is .9, below 1 We also observed a preliminary signal very early on for GBS This was at the second look where we observed three events within the Shingrix group compared to less than one event expected based on historical data The relative risk estimated at that time was over five And as you can see now, that effect has also attenuated considerably The relative risk is currently estimated based on these data at 1.24 It is only based on about six presumptive adverse events however, and so there’s considerable uncertainty in this estimate Next slide We did considerable further follow up on the preliminary GBS signal we found when using the ICD 10-based coded definition, and in particular we conducted physician chart review to determine the truth GBS status

for these six presumptive cases And so among those six, three of them were ruled out as they had symptoms prior to vaccination And three were confirmed, two as Brighton level two and one as Brighton level three And we also conducted chart review Among the historical cases, there were five such cases Two of those were ruled out One was unable to be validated, there wasn’t enough information to make a diagnosis, and two were confirmed, both at Brighton level two And so based on our chart validated outcome data, our best current estimates in the VSD of the relative risk are either 1.55 if we assume that two of those five ZBL cases are confirmed, or 1.03 if we assume that all three of those cases were confirmed So basically a sensitivity analysis here that, depending on how you classify that one missing, confirmed case, next slide So in summary, after receipt of about 650,000 doses of RZV in the VSD between January 2018 and December 2019, we found a preliminary signal for Bell’s palsy, but the effect did not persist as we accrued more doses A preliminary signal was also observed for GBS, an effect that also waned over time With chart review to confirm the true case status for GBS, we found that VSD is not in a position to have sufficient evidence to determine whether or not there’s an increased risk of GBS The relative risk that we can estimate based on these data is 1.55 But the confidence intervals, as you can see here, are very wide and cross one going from about zero to almost 18 And so overall, we don’t have sustained evidence of increased risk among RZV recipients for any prespecified outcome that we have followed We have done considerable subgroup and secondary analysis that provide further reassurance of these primary results that I’ve shown today Thank you >> Thank you for your presentation Dr. Nelson Do we have any questions from the voting members? Or from the liaisons? Dr. Atmar, please? >> Yes, thank you for a very nice presentation Can you remind us how you get the expected number that is a comparator? >> Sure. So these are historical comparators who have received zoster vaccine live in the five years prior to the uptake period for Shingrix So the primary analyses are based on numbers of events that we observe in that population And then they’re adjusted for age, gender, site and for our cardiovascular outcomes for a couple of other factors to equalize between groups But these results don’t fully adjust for all the confounders That’s analysis that we currently have in progress using end of study cumulative data And we’re conducting additional analyses that use comparator group other than the historical group >> Thank you So it would not account for some other event that might be going through the community that could be associated with GPS? Is my understanding correct? >> Can you say more about what you mean? >> So for example, if in the community that were being surveyed during the period of surveillance, there was some other infection say that was going through the community and was associated with GBS — I guess, let me re-ask the question Is the control group a contemporaneous group that would take into account environmental and other issues going through the communities at the time? Or as I understood it, it’s instead a historical group that might not account for environmental events, other infections that might be associated with GBS >> Sure, I understand your question now Thank you So this is — you’re right This is a historical comparator group, so any other changes over time during the period prior to Shingrix uptake compared to during Shingrix uptake, we can’t untangle those differences — differences that we might observe between the vaccine groups could be due to other things that change during those two periods of time And that’s why in our end of study analysis we are using contemporaneous control groups such as people who received well visits during the Shingrix period, and also had a flu vaccine in the prior year, or received other vaccinations during the Shingrix period So and those results provide us with similar information

as what I’ve shown you today And so we’ve done a couple of — several different analyses to manage different biases that exist depending on the type of observational study design that we use So we feel pretty good about the robustness of the findings we have here that I presented today >> Thank you >> Any other questions from the liaisons or from the voting members? Seeing none, we’ll proceed to the next set of talks So Dr. Tara Anderson will be talking about the risk of Guillian-Barre syndrome following herpes zoster, and then a summary and planned risk benefit analysis regarding use of RZV in immunocompetent adults We’ll hold questions until the end of the second presentation Dr. Anderson if you please >> Okay. Thank you, Dr. Romero And thank you to Drs Lee, Sue and [inaudible] and Nelson for your presentations I will now present a CDC led analysis of the risk of Guillian-Barre syndrome following herpes zoster First for some background Guillian-Barre syndrome or GBS is a rare immune mediated disease of the peripheral nerves In the United States, the estimated annual incidence of GBS across all ages is one to two cases per 100,000 persons Risk factors for GBS include increasing age, male gender, immunocompromised status, previous viral and bacterial infections, and recent vaccinations, for example, some influenza and rabies vaccines Tegarding previous infections, the strongest evidence in the literature is for the viral and bacterial pathogens listed here As the ACIP herpes zoster workgroup discussed RZV post licensure safety monitoring results, it was noted that in some instances both disease and vaccination have been associated with GBS For example, as with influenza virus infection and some influence of vaccinations Therefore, the group agreed it would be important to further explore the risk of GBS following herpes zoster A possible temporal association between herpes zoster and GBS has been noted in a small number of case reports in the literature And one previous epidemiologic study by Kung, Shu and Lin reported an increased risk of GBS following recent zoster In this population-based cohort study using Taiwan’s national health insurance research database, the investigators found 0.03% of patients develop GBS within two months following zoster And the adjusted hazard of GBS during the follow up period was 18.37 times greater for patients with herpes zoster than those without zoster To our knowledge, there are no published epidemiologic studies in other settings or using other methods We therefore conducted a case series study designed to strengthen our epidemiologic understanding of the risk of GBS following herpes zoster, and help clarify the benefits versus potential risks of vaccination The primary objective of the analysis was to evaluate the risk of GBS following herpes zoster using a self-control case series analysis of healthcare claims data from two large national data sources And the secondary objective was to describe characteristics of these GBS cases, including demographics and outcome severity, such as duration of GBS hospitalization, and ICU admission I will now provide some brief background on the study methodology The self-control case series method was developed in 1995 for use in vaccine safety studies And it has since been broadly applied in epidemiology This approach is used to examine the temporal association between a transient exposure such as herpes zoster, and a subsequent event such as GBS The precise timing of the exposure and the event is important Only individuals with both the exposure and the event of interest are included in the analysis Each case serves as their own control, therefore, confounding by time invariant factors is eliminated The self-control case series method estimates the relative risk of rates and the risk window compared to rates in the control window We used two data sources for this study The first was the IBM market scan commercial databases, which include individual level deidentified healthcare claims for persons covered by employer sponsored insurance The market scan commercial data are a convenient sample drawn from IBM Watson health clients, which include approximately 30-50 million persons enrolled annually since 2006 The second data source was the CMS Medicare databases, which include individual level deidentified healthcare claims information for Medicare beneficiaries

The CMS Medicare data included 100% sample of all fee for service clinical claims data for Medicare for approximately 50-60 million Medicare enrollees annually Approximately one-third of Medicare beneficiaries are covered under Medicare Parts A, B and D fee for service For our study populations from the market scan commercial databases, we included all persons 18 to 64 years of age during 2010 to 2018, for whom outpatient pharmaceutical claims data were available From the CMS Medicare databases, we included all persons 65 years and older during 2014 to 2018, with enrollment and Medicare Parts A, B and D. Of note, no drug data were available prior to 2014 In addition, we did not include beneficiaries enrolled in Medicare Part C, or Medicare Advantage managed care plans since drug claims data were not available for this population For both data sources, persons included in the analysis had to be enrolled for — excuse me, from 180 days before through 365 days after herpes zoster In the next few slides, I will summarize our study definitions Herpes zoster cases were defined as persons with an outpatient claim with a primary or secondary ICD 9 or ICD 10 diagnostic code for herpes zoster Since we wanted to capture incident zoster cases, we excluded persons in whom their first herpes zoster diagnostic code was a post herpetic neuralgia or PHN code We did retain persons with subsequent PHN codes We also excluded persons with a claim for zoster vaccine, either Zostavax or Shingrix within one day of their zoster diagnostic code, because this may more likely represent instances of miscoding The herpes zoster index date was defined as the date of the first herpes zoster claim during the study period For GBS, cases were defined as persons with an inpatient claim with a principle diagnostic code for GBS To increase the specificity of the GBS diagnostic code, we required it to be paired with a procedural code for lumbar puncture, electromyography or a nerve conduction study, procedures which are typically part of the diagnostic procedures for patients with GBS We excluded persons with GBS in the 180-day window prior to zoster, and excluded persons with previous infections or Shingrix vaccination during the 42-day period prior to GBS These infections included the previously noted viral infections of CMV, Epstein-Barre virus, influenza, hepatitis E and Zika, and the bacterial infections Campylobacter jejunae and mycoplasma pneumoniae that currently have the strongest evidence of association with GBS We also evaluated several negative controls to validate our methods We selected conditions that were similar to GBS and that they are acute conditions with an abrupt onset and a low rate of reoccurrence We also selected these conditions because they were not expected to increase after herpes zoster These negative controls included appendicitis, nephrolithiasis, colocystitis and fractures of the upper limb And these were defined based on ICD 9 and ICD 10 codes We excluded persons with claims for these conditions and the 180-day window prior to zoster As previously noted, we chose the self-control case series design, in which only cases are included in the analysis and each case serves as their own control In this analysis we compare the rate of GBS or negative controls and the risk window as compared to the rate in the control window The risk window for this study was the one to 42-day window after the herpes zoster index date, which is comparable to the period typically used in vaccine safety studies We selected two control windows The primary control window was the 100-365-day period from the zoster index date And the secondary control window was the 43-99-day period from the zoster index date We used conditional Poisson regression to compare rates of visits in the risk window versus the two control windows Now I will address the study results We identified a total of 489,516 persons with herpes zoster aged 18 to 64 years from the 2010 to 2018 market scan commercial data, among whom 11 developed GBS during the 100-365 days following herpes zoster We identified a total of 650,229 persons with herpes zoster aged 65 years and older from the 2014 to 2018 CMS Medicare data, among whom 41 developed GBS during the 100-365 days

following zoster The available age breakdown by data source is provided here For the CMS Medicare data, cell sizes smaller than 11 are suppressed For those 18 to 64 years, there’s a slightly higher percentage of cases aged 50 to 64 For those 65 years and older, the highest percentage of cases was in the 70 to 79-year age range For those 18 to 64 years 82% of GBS cases were female And for those 65 years and older 54% of GBS cases were female Regarding the interval between herpes zoster and GBS for those 18 to 64 years, a higher proportion of GBS cases occurred within the first 42 days after zoster compared to the primary control window For those 65 years and older, we observed a higher proportion of GBS cases within the risk window and secondary window compared to the later primary control window Regarding duration of GBS hospitalization and ICU admission, we identified evidence of more severe GBS among those 65 years and older, with a median duration of hospitalization of nine days, and 51% admitted to the ICU For the self-control case series analysis, the rate ratio of GBS was increased during the 42-day risk window following herpes zoster, as compared to the primary control window for both age groups, with a rate ratio of 6.3 for those 18 to 64 years of age, and a rate ratio of 4.1 for those 65 years and older For both age groups, the rate ratios during the 42- day risk window following zoster compared to the secondary control windows were not statistically significant, given the noted confidence intervals For those 18 to 64 years of age, the rate ratios of the negative controls were not increased during the 42-day risk window as compared to either control window These values range from 0.9 to 1.2 in the primary control window and 1 to 1.3 in the secondary control window Given the confidence intervals, these values were not statistically significant For those 65 years and older, the rate ratios of the negative controls during the 42-day risk window as compared to the control windows ranged from 1 to 1.4 in the primary control window and 0.9 to 1.5 in the secondary control window Although some confidence intervals indicated statistical significance, all negative control values were much lower than the rate ratio of 4.1 observed for GBS in this age group during the 42-day risk window as compared to the primary control window There are several strengths and limitations for this study Regarding strength, we use large national datasets that include medical and pharmacy claims The self-control case series design inherently controls for potential confounders, such as gender and underlying medical conditions, and each case serves as their own control The study inclusion criteria strengthened herpes zoster and GBS case identification, and the exclusion criteria accounted for potential confounders such as antecedent for previous infections Regarding limitations, we identified a small number of GBS cases in both data sources Market scan is a convenient sample and it’s not nationally representative And there is the potential for miscoding or misclassification bias in claims data And finally, we were unable to validate GBS, herpes zoster or other diagnoses using medical record review So in conclusion, in the self-control case series analysis, we identified an increased risk of GBS in the 42-day window following herpes zoster, compared to the primary control window of 100 to 365 days This increased risk was identified across adult age groups, and in two different large administrative data sources The negative control results strengthened our findings The negative control rate ratios clustered around the null effect of one with a range of 0.9 to 1.4 for the primary control window, and these values were lower than rate ratios for GBS identified in both data sources Finally, we identified evidence of more severe GBS in terms of longer duration of hospitalization and a higher percentage admitted to the ICU among those 65 years and older I would like to acknowledge my coauthors, Jessica Long, Dr. Rafael Harpaz and Dr. Kathleen Dualing for their collaboration on this work, and the ACIP herpes zoster workgroup for their valuable feedback Thank you >> Thank you very much for that extensive presentation,

Dr. Anderson I’d just like to say to the members and to liaisons, the presentation of this data and the extensiveness of the data really serves to exemplify the degree and the type of collecting systems we have for vaccine safety in this country And I think it bodes well for the future with regard to monitoring for newer vaccines that will be coming out So thank you very much for presenting this So I’ll turn this over to the voting members to see if there are any questions Please raise your hands if there are I see Dr. Lee has a question >> Oh, just I was hoping we might be able to actually go through her last presentation and then take questions all at once if that’s okay, Jose >> Sure. We can do that Go ahead, Dr. Anderson >> Thank you If we can have the next presentation, please Thank you Okay, excellent Thank you I will now provide a summary of the session and ACIP herpes zoster workgroup discussions as well as next steps including a planned risk benefit analysis regarding the use of recombinant zoster vaccine in immunocompetent adults Before I begin though, the herpes zoster workgroup would like to thank the Immunization Safety Office, as well as the Vaccine Safety DataLink and the FDA for their contributions toward monitoring recombinant zoster vaccine safety The workgroup would also like to thank many CDC and other contributors who have provided valuable contributions and insight Two critical RZV safety monitoring updates from VAERS and VSD were shared during today’s session As discussed by Dr. Sue and Dr [inaudible] regarding VAERS, serious adverse events have rarely been reported, and RZV post licensure safety monitoring findings in VAERS are generally consistent with the safety profile observed in pre licensor clinical trials As discussed by Dr. Nelson regarding the vaccine safety DataLink rapid cycle analysis conducted based on data from January 2018 through December 2019, results from the final chart confirmed analysis indicate the VSD has insufficient evidence to determine if there’s an increased risk of GBS As was presented during the June 2019 ACIP meeting, FDA has conducted assessments of the risk of GBS following RZV in Medicare data in collaboration with CDC and CMS The preliminary results of the cohort analysis presented at that meeting, which compared the postvaccination GBS rate between persons 65 years and older who received recombinant zoster vaccine between October 2017 and December 2018, and historical controls who received Zostavax or ZVL between October 2012 and September 2017 indicated an elevated adjusted rate ratio of 2.34 On the advice of the herpes zoster workgroup, FDA conducted additional analyses using self-control case series methods The FDA has additional results available from the claims faced, self-controlled analysis and the medical record review of self-controlled analysis These results are currently under review at FDA and will be shared at a future ACIP meeting As discussed during my previous presentation, a possible temporal association between herpes zoster and GBS has been noted in a small number of case reports, and one previous epidemiologic study reported increased risk of GBS following recent herpes zoster In the CDC led self-controlled case series analysis, we identified an increased risk of GBS one to 42 days following zoster compared to the primary control window of 100 to 365 days across adult age groups and in two different administrative data sources I will now provide a brief summary of the herpes zoster workgroup discussion since the June 2019 ACP meeting The workgroup is currently reviewing evidence regarding the use of recombinant zoster vaccine in immunocompromised adults The workgroup is concurrently reviewing and discussing findings regarding the possible risk of GBS following both disease and vaccination, and agrees that continued safety monitoring of RZV in VAIRS and VSD is warranted In addition, a dynamic risk/benefit assessment that incorporates new data on risk of GBS associated with disease and vaccination will inform recommendations on the use of RZV in immunocompetent and immunocompromised adults This planned risk/benefit analysis will evaluate the benefits of averted herpes zoster cases and complications versus risk, excuse me, of adverse events Subject matter experts and the herpes zoster workgroup will collaborate on model parameters and scenarios

And the outcomes per 1 million vaccinated individuals to be estimated would include episodes of herpes zoster, episodes of pos herpetic neuralgia and other zoster complications such as GBS, injection site reactions, systemic reactions, and rare adverse events such as GBS Regarding next steps, we look forward to the discussion of today’s presentations In addition, the herpes zoster workgroup is committed to providing updates to the ACIP at the earliest opportunity Future meeting presentations will address FDA’s assessments of the risk of GBS following RZV in Medicare data, the results of the risk benefit analysis regarding use of RCZV and immunocompetent adults, and recombinant zoster vaccine use in immunocompromised adults During our discussion, we would appreciate feedback from ACIP on the following questions Does ACIP have any other suggested follow up regarding RZV safety monitoring? And does ACIP have any feedback on the planned risk benefit analysis for use of recombinant zoster vaccine in immunocompetent adults, particularly any other outcomes of interest? Thank you very much for your time and attention I’ll now turn back to Dr. Romero >> Thank you Open for questions from liaisons and from voting members Dr. Talbot >> This has been an amazing amount of work that’s been shown today And I have been trying to filter through all this information as quickly as possible And I want to make sure I’ve done it correctly since I’ve done it quickly Are we saying that there is a signal following vaccination that we’re not yet clear if it’s a random occurrence or a true event? >> Based on the results to date, the safety profile’s reassuring We are continuing to follow up given the previous results from the FDA analysis showing an elevated adjusted risk in the Medicare data And also given the study results that I just presented regarding the risk of GBS, that’s also been noted for an association with GBS >> Okay, so I guess regardless of GBS associated with herpes zoster, the numbers that you showed did not show — no risk after vaccination, unless I misread that Is that correct? >> That’s correct >> Okay. We talk about GBS as one in a million for influenza? Can you give me an idea of that number for the current shingles vaccine? >> Not at this time The results that have been shared to date are related to the information that I shared on the slides, based on the RZV versus the ZVL comparator group So the elevated adjusted ratio of 2.34 >> What are the plans for the future studies and future evidence to be brought to ACIP? >> The FDA intends — yes, the FDA intends to present at a future meeting the results of their self-controlled case series analyses Those results, as I mentioned, are under review at this time with FDA and they’ll share them as soon as possible >> Okay I guess I’m slightly hesitant that this is a vaccine with a very powerful adjuvant And I think with the prior record recommendation for preferential use, the prior vaccine is no longer available, or will no longer be available after — >> Dr. Talbot, I’m going to interrupt you for just a second because Dr. Messonier wants to make a comment >> Actually, I want to make sure that I’m articulating it — and I’m sorry, it is so hard in this virtual environment So I want to make sure that we’re answering your question appropriately and I kind of think I know where you’re going But I’m going to ask our subject matter expert

There are two studies that show a positive signal But you don’t actually — haven’t completed the risk/benefit evaluation that would get to the additional risk of GBS compared to the risk of prevention of zoster And there’s a third study that FDA is doing that we expect and hope to have before February, is that correct? Or if not, please, correct me because I may not be right >> Yes. So as Dr Nelson shared today, the results of the VSD analysis indicated initially there was a signal for GBS, but over time that signal has attenuated So now the results of that study do not indicate — they don’t have sufficient evidence to, you know, say that there’s a signal in VSD In VAERS there has not been a signal In the initial results that have been presented to date by FDA, their initial cohort analysis, there was an adjusted risk, elevated risk in the RZV versus the ZBL comparator group And so that is what’s been presented to date The results of their self-controlled case series analyses also using Medicare data will be presented at another time They’re currently under review at FDA So yes, we’re waiting on the results of those analyses And then in the meantime, what we’re also discussing doing from the workgroups recommendation is to move forward with this planned risk/benefit analysis, where we would be taking into consideration new information that would be related to the possible risk of GBS after vaccination, as well as the risk of GBS after infection So I hope that clarifies things >> Before we go back to Kim, I’m going to ask you another question >> Sure >> I think she’s asking, what is the upper bounds of the potential increased risk? So in other words, GBS is one in a million I know that there are still data, but I think she’s trying to get to what’s the absolute maximum risk? In other words, is there enough data to be concerned enough to act now as opposed to waiting for additional analysis? >> At this point, I don’t believe that we’ve had sufficient evidence or sufficient information presented in order to be able to determine that So yeah Thank you >> Dr. Talbot? >> Thank you, Dr. Messonier I appreciate that I will be looking forward to your data >> Thank you >> All right Very good Dr. Lee >> Yes, thank you I just wanted to also be able to respond So I’ll just kind of repeat the summary just so we’re all on the same page So first, I wanted to emphasize what Dr. Romero said, which is that we absolutely rely on our vaccine safety surveillance systems to detect signals These signals in VAERS and — well, these signals in VSD was presented previously, and also the surveillance from VAERS was presented previously And long-term sort of — not on long-term On follow up of those signals, those signals have attenuated in those databases over time We are waiting for the FDA CMS analysis Obviously, that database has the greatest power to be able to give us the information needed, in addition to you know — at that time, we were focused on making sure that these cases are validated So the way I would frame this is that if you’re thinking about signals — we detected a statistical signal And after a statistical signal is identified, we would go on to conduct signal refinement activities and signal evaluation activities And those activities are underway in several systems Today, you heard that the VAERS and VSD systems, those signals are not identified in VAERS and have attenuated in VSD We are looking forward to seeing the FDA CMS data again, because they have a large proportion of older adults who are receiving these vaccines And so I think that will be very helpful to ensuring that we are making decisions based on the best possible data So that’s part one Part Two, I think, you know, also really important was this analysis of GBS following disease And I have to say that I had not intuitively understood the high rate of GBS following herpes zoster infection I had appreciated it following campylobacter or other types of infections, but I had not had this on my radar The reason I think that’s important and I want to call that out, is because it’s different than the way we’re used to thinking about vaccine safety, which is against the background of a general population I think it’s really important to remember that the benefit/risk analysis is really around people

who get the disease and people who are vaccinated So having the rates of GBS following herpes zoster infection is actually incredibly helpful to help understand the benefit/risk balance in the population, particularly for this vaccine We absolutely at the workgroup think that the vaccine safety needs to undergo continued monitoring Brought these results today, which is a lot of information, agree, regarding where we are in terms of the vaccine safety evaluation, as well as evaluation following disease Because we think it’s so important from a transparency perspective to bring all this data to ACIP We anticipate more data will be forthcoming But the reason we’re proposing this benefit risk analysis is because of both the statistical signal that’s continuing to undergo evaluation, as well as this new information regarding the risk of GBS following herpes zoster infection And to your point, I think that is exactly what we want to bring to ACIP for discussion >> Thank you Dr. Bell? >> Thanks I just wanted to add a little bit to this discussion and make two points The first being to just echo how important what you said, Dr. Romero and also Dr Lee, about the importance of these safety monitoring systems for all of our new vaccines And in that context, I think, you know, we do want to remember that we have been evaluating this signal, but the evaluation is ongoing And, you know, I think this sort of issue needs to be worked out over time You need to keep looking at it as more people get vaccinated And, you know, address signals as they arise And perhaps the signal for GBS will change over time And that’s what we’re, you know, we’re looking for that The other point is that another potential benefit of doing a risk/benefit analysis is a sensitivity analysis that could be part of the process that might help with, you know, some of the questions, for example, around what Dr. Talbot is asking That is, you know, what’s the upper bound? Where would this risk/benefit balance shift with respect to, for example, in association between vaccination and GBS? So I think there’s benefit to using this risk/benefit analysis partially as another way of exploring the meaning and the potential impact of these signals as they arise >> Thank you, Dr. Bell Next, Dr. Hunter >> Thanks I’m very reassured by the data that’s being presented right now And I’m the person that voted against the preferred recommendation And I think I’m almost to the point — I think I need more data But I’m almost to the point where I could say to my patients, 50-year-old patients who are coming, asking about, you know, they’ve heard that, you know, there might be the signal on GBS with a vaccine — to say what I generally say for influenza vaccine Which is, you know, you’re actually going to be at lower risk if you get the vaccine, because you’re going to protect against getting herpes zoster outbreak So I don’t know if that’s — you know, I’m a clinician I’m looking at this data without the sophisticated eye of cost/benefit analysis that Dr. Lee and others who do research like Dr. Talbot But I think that this initial data is very reassuring to me So I just want to mention that >> Thank you, Dr. Hunter Miss McNally >> Thank you I’m just wondering, so consumers understand when you estimate timing wise and update on the risk/benefit analysis, as well as the FDA assessment? >> Yes, we anticipate presenting those as soon as possible at an upcoming meeting of the ACIP Yes, ideally, February >> Thank you >> Yes, February >> Are there any other questions from the voting members? Do any liaison members have a question or comment? Dr. Anderson, Dr. Lee, questions were posed at the end of your presentation Did we provide you with the information that you wanted at the very end? >> Oh, I see here >> Yeah >> Well, as I mentioned, we just wanted to make sure that the ACIP members, if they did not have any other suggested follow up regarding the safety monitoring or any particular feedback Regarding [inaudible]

So it doesn’t sound like there’s anything >> Very good Thank you I just wanted to make sure >> Thank you >> All right Sorry, Dr. Cohn wants to make a comment >> Yeah, I just want to add to reassure everyone as well, when the FDA data are available for review on the workgroup, if there’s concerning data that would necessitate needing to meet earlier in order for the ACIP to review the data before February, that can absolutely be done Over >> Thank you All right, then we’re a little early, but we’ll break now for lunch and return at 20 after the hour for tick-borne encephalitis vaccine introduction by Dr. Poeling So enjoy your lunch and we’ll see you all in a little while