01 MPOX Rao 508

Clade I Mpox Outbreak:
Situational UpdateCenters for Disease Control and Prevention
Agam Rao, MD
CAPT, U.S. Public Health Service
Chief Medical Officer, Poxvirus and Rabies Branch
ACIP meeting
Oct 24, 2024
2Clade I MPXV:
Countries
known for
decades to be
endemicDemocratic Republic of the Congo (DRC), Central
African Republic, Republic of Congo, Cameroon,
Gabon
•Exposure to infected wildlife
•Person -to-person spread
-Skin-to-skin contact (including intimate or sexual contact)
-Direct contact with respiratory secretions (e.g., via kissing)
-Direct contact with contaminated objects (e.g., shared towels, bedding)Monkeypox virus (MPXV) Transmission
Clade I Outbreak in DRC, 2023 -present
•Reason for concern
▪High number of suspect cases
▪Laboratory confirmed cases identified in
provinces previously without cases
•At least two concurrent outbreaks
▪Clade Ia (e.g., Equateur Provence in western
DRC): Mortality rate historically reported as
1.4-11%; however, NIH trial in DRC indicates
routine supportive care led to mortality rate
of ~1.7%*
▪Clade Ib (e.g., Sud Kivu in eastern DRC): Seems
to cause less severe disease than clade Ia;
mortality rate <1% in DRC
*https://www.nih.gov/news -events/news -releases/antiviral -tecovirimat -safe-
did-not-improve -clade -i-mpox -resolution -democratic -republic -congohttps://www.who.int/emergencies/disease -outbreak -
news/item/2024 -DON522

•Clade Ia: multifactorial
-From animals to people: high proportion of cases in children
-Human -to-human spread in households: both adults and children
-Sexual contact, regardless of sexual orientation and gender identity: adults
•Clade Ib: Sexual contact comprises large proportionHow Clade I Mpox is Spreading in DRC*
*Based on what is known at this time
Cases Outside of DRC
•Clade Ia: Only detected in
endemic countries (Central
African Republic and Republic of
the Congo)
•Clade Ib:
▪Associated with sustained
spread: Burundi, Uganda,
Rwanda
▪Not associated with sustained
spread: Kenya, Thailand, Sweden,
India, Germany
https://wwwnc.cdc.gov/travel/notices/level2/mpox -drc-neighboring -countriesList of countries with sustained spread maintained here:
https://www.cdc.gov/mpox/vaccines/index.html https://emergency.cdc.han/2024/han00513.asp
•Primarily via sex (e.g., transactional sex) while visiting countries with sustained
transmission
•Secondary spread
-Limited (if any) in several non -endemic countries (e.g., Thailand, Sweden, India)
-Uncertain at this time in some countries but believed to be associated with close
household contactHow Clade I Mpox is Spreading to Non -
Endemic Countries*
*Based on what is known at this time
Laboratory Confirmed Clade I Mpox
Cases During 2024 (As of 13 October)
*Only ~20% of suspected cases are laboratory confirmed; total DRC population = >110 million people
†Many are cases among children; no deaths
§Death in an individual with underlying health conditions and may not be due to mpox
https://worldhealthorg.shinyapps.io/mpx_global/#24_Data_by_countryCountry Total casesCase
fatality
ratio (%)Cases in
2024Deaths
in 2024Cases in the
past six
weeks1Deaths
in the
past six
weeks1Clades
detected in
countryDate of last
reported
case
The Democratic
Republic of the Congo8,207* 0% 6,962 25 1914 0 Clades Ia and Ib 13-Oct-24
Central African Republic 104 2% 57 1 10 0 Clade Ia 29-Sep-24
Republic of Congo 48 4% 22 0 1 0 Clade Ia 29-Sep-24
Burundi 1,169 0% 1,169 0† 841 0 Clade Ib 13-Oct-24
Uganda 91 0% 91 0 76 0 Clade Ib 13-Oct-24
Kenya 13 8% 13 1§ 9 1 Clade Ib 13-Oct-24
Rwanda 6 0% 6 0 2 0 Clade Ib 15-Sep-24
9Clade I Mpox Cases and the United States
No Clade I Cases in the United States*
*Active surveillance conducted via clade -specific testing of high proportion of MPXV positive specimens, including those tested in commercial laboratories
•Pre-travel counseling about risk reduction strategies
-Avoid close contact with people sick with signs and symptoms of mpox, including
skin or genital lesions
-Avoid contact with contaminated materials used by people who are sick (e.g.,
clothing, bedding)
•Vaccination, irrespective of sexual orientation and gender identity, for
travelers to certain countries* who  anticipate any of the following during
travel
-Sex with a new partner
-Sex at a commercial sex venue (such as a sex club or bathhouse)
-Sex in exchange for money, goods, or other trade
-Sex in association with a large public event (such as a rave, party, or festival)Risk Considered Low for U.S. Travelers
*List of countries maintained here: https://www.cdc.gov/mpox/outbreaks/2023/index.html https://emergency.cdc.gov/han/2024/han00516.asp
•Even in extreme scenario (e.g., household secondary attack risk of 30%,
double the previously considered worse case scenario)†
-Most simulated outbreaks were small (66% had ≤ 5 cases and 73% had ≤10 cases)
-Most simulated outbreaks had minimal spread between households (72%
affected ≤ 3 households)
•Modeling suggests that even with extremely high secondary attack risk,
household clusters (including cases in children) would most likely involve 10
or fewer MPXV clade I cases, with limited spread between households
•Based on what we know today and current characteristics of viral spread,
do not expect children to be heavily impacted if clade I diagnosed
domestically §Risk Considered Low for General U.S.
Population*
*https://www.cdc.gov/cfa -qualitative -assessments/php/data -research/mpox -risk-assessment/index.html
† https://www.cdc.gov/cfa -modeling -and-forecasting/mpox -transmission -technical -brief/index.html and unpublished data
§ https://www.cdc.gov/mpox/php/data -research/clade -i-mpox -in-children -in-africa -and-potential -impacts -on-children -in-the-
united -states.html
13What CDC and Other U.S. Government
Partners are Doing
•Providing technical assistance and funding to DRC’s Ministry of Health
• Working with USAID, WHO, International Organization for Migration,
African Field Epidemiology Network, and other partner teams on the
ground to help manage outbreaks
•Collaborating with public health officials in several countries bordering DRC
to assess needs and provide support for outbreak preparedness
•Donating 1 million doses of JYNNEOS vaccine and $500 million for supportInternationally
•Increasing capacity to rapidly detect, contain, and manage clade I cases
should they occur domestically
•Increasing capacity to detect cases of clade I and clade II mpox through
existing surveillance systems, including wastewater testing in communities
across the United States and in select airports
•Coordinating with state, tribal, local, and territorial public health
departments to provide clinical, diagnostic, and other guidance
•Raising awareness: Regular communications and updatesDomestically
* https://www.cdc.gov/nwss/wastewater -surveillance/mpox -data.html
•High number of suspected clade I mpox cases in DRC; ~20% are laboratory -
confirmed
•Travel -associated spread of clade Ib to some countries
-Cases milder than those associated with clade Ia
-Predominantly associated with sex (e.g., transactional sex) with subsequent
spread to others (e.g., children) likely via household contact
•Risk to U.S. travelers low but counseling and vaccination should be provided
to travelers
•Impact to persons in the United States (including children) expected to be
low Summary*
*Conclusions are based on investigations and other data available to CDC at the time this presentation was given;
findings and CDC guidance may change over time
17ACIP
•Reforming
-Dr. Bonnie Maldonado, Workgroup chair
-Dr. Faisal Minhaj:  Workgroup lead
•Workgroup charge
-Review NIH study about use of JYNNEOS in persons 12 -17 years of age
-Consider bringing to an ACIP vote, use of JYNNEOS in persons 12 -17 years of age
at risk for mpox during mpox outbreaks (including the global clade IIb outbreak)
•Anticipating presentations (including Terms of Reference) during February
2025 ACIP meeting
•Planning publication of ACIP recommendations for persons 12 years of age
and older in one consolidated MMWRWorkgroup
The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the Centers for Disease Control and
PreventionThank you
19
poxvirus@cdc.gov

Summary: Clade I Mpox Outbreak:   Situational UpdateCenters for Disease Control and Prevention Agam Rao, MD CAPT, U.S. Public Health Service Chief Medical Officer, Poxvirus and Rabies Branch ACIP meeting Oct 24, 2024 2Clade I MPXV:  Countries  known for  decades to be  endemicDemocratic Republic of the Congo (DRC), Central  African Republic, Republic of Congo, Cameroon,  Gabon •Exposure to infected wildlife •Person -to-person spread -Skin-to-skin contact (including intimate or sexual contact) -Direct…


01 RSV Adult Kotton 508

1
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Adult Respiratory Syncytial Virus (RSV) Session
Camille Kotton, MD
Chair, Adult RSV Work Group
Advisory Committee on Immunization Practices (ACIP)
June 26, 2024
2Adult RSV Work Group Membership
ACIP Voting Members
Camille Kotton (Chair)
Keipp  Talbot
Sarah Long
Albert Shaw
Ex Officio Members
Rachel Zhang (FDA)
Nicholas Geagan (FDA)
Nadine Peart Akindele (FDA)
Sonnie Kim (NIH/NIAID)
Michelle Juaneza (HRSA)
Uzo Chukwuma (IHS)CDC Co -Leads
Michael Melgar
Amadea BrittonConsultants
Robert Atmar (Baylor College of
Medicine)
Doug Campos -Outcalt (University of
Arizona)
Helen Chu (University of Washington)
Peter Donofrio (Vanderbilt University)
Marie Griffin (Vanderbilt University)
Rebecca Morgan (Case Western Reserve
University)
Cynthia Lucero -Obusan  (Veterans Health
Administration)
Tracy Ruckwardt (NIH/NIAID)
Jonathan Temte  (University of Wisconsin)Liaisons
Kenneth Schmader (AGS)
Vidya Sundareshan (ACP)
Gretchen LaSalle (AAFP)
April Killikelly (NACI, PHAC)
Winnie Siu (NACI, PHAC)
Katherine Williams (APTR)
Ruth Lynfield (NFID)
Bindy Crouch (AIM)
Steven Pergam (IDSA)
Elizabeth Skoy ( APhA )
3▪Dr. Albert Shaw will be the incoming work group chair for the adult RSV work group
starting in July 2024. Transition in Work Group Chair
4Melissa Coughlin
Fatima Dawood
Katherine Fleming -Dutra
Kristen Folsom
Jarrett Gartin
Monica Godfrey
Aron Hall
Fiona Havers
Michele Hlavsa
Jefferson Jones
Ruth Link -Gelles
Agustin Lopez
Josephine Mak
Meredith McMorrow
Noelle -Angelique MolinariDanielle Moulia
Ismael Ortega -Sanchez
Lakshmi Panagiotakopoulos
Pragna Patel
Monica Patton
Amanda Payne
Derrell Powers
Mila Prill
Lauren Roper
Diya Surie
Natalie Thornburg
Raigan Wheeler
Megan Wallace
Trang WisardCDC Contributors
Immunization Safety Office
Anne Hause
Pedro Moro
Christine Olson
David Shay
Karen Broder
John Su
Eric Weintraub
Michael McNeil
Julianne GeeImmunization Services Division
Carla Black
Kayla Calhoun
Jennifer Kriss
James Singleton
Nicole Dowling
Andrew Leidner
Jamison Pike
James Singleton
Patricia Wodi
Influenza Division
Jill Ferdinands
Lisa GrohskopfNCIRD Office of the Director
Hannah Rosenblum
Melinda Wharton
Jessica MacNeilCoronavirus and Other Respiratory Viruses Division
5▪ACIP voted on this recommendation at the June 2023 meeting
▪Recommendation is not product -specific; administer whichever vaccine is availableCDC and ACIP currently recommend that adults aged 60
years and older may receive a single dose of RSV
vaccination, using shared clinical decision -making.
https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm
6▪Moderna presented safety and efficacy data from the first 9 months of follow up in their phase 3
trial in adults aged ≥60 years
▪CDC presented risk -stratified rates of RSV -associated hospitalization in U.S. adults aged 50
years and older
▪CDC gave an update on uptake and implementation of RSV vaccine in U.S. adults aged 60 years
and older during the first season following the recommendation
▪CDC and FDA presented on post -marketing safety of the protein subunit RSV vaccines (GSK’s
AREXVY and Pfizer’s ABRYSVO) in adults aged 60 years and older
▪CDC presented an analysis comparing the estimated magnitude of public health benefit and
potential risk of Guillain -Barre syndrome (GBS) associated with protein subunit RSV vaccination
in adults aged 60 years and older
▪For adults aged 60 years and older who remain unvaccinated, ACIP agreed with encouraging
timing of RSV vaccination in the late summer and early fall to optimize public health benefitsRecap of Adult RSV session, February 2023
7▪Moderna mRESVIA  for use in adults aged 60 years and older (received FDA approval
May 31, 2024)
▪GSK AREXVY for use in adults aged 50 -59 years at increased risk of severe RSV disease
(received FDA approval June 7, 2024)
▪Continued discussion of safety, including risk of GBS, following RSV vaccination
▪Shift from a shared clinical decision -making recommendation to:
–Potential universal recommendation in adults 75 and older
–Potential risk -based recommendation in adults 60 –74
–Potential risk -based recommendation in adults 50 –59Recent work group discussion
8▪In June 2023, ACIP recommended RSV vaccination in adults 60 and older using shared
clinical decision -making
–In addition to benefits of vaccination, the shared clinical decision -making discussion, as intended by ACIP , is also
meant to include discussion of the potential risk of vaccine -associated adverse events associated with RSV
vaccine, specifically Guillain Barre Syndrome.
▪In the first year following this recommendation, we have learned:
–Feedback from healthcare providers that having SCDM conversations is not simple in practice.
–Unlike a universal recommendation where there’s a clear call to action to vaccinate, with SCDM the call to action
is to discuss with a healthcare provider, a less clear message.
▪A risk -based recommendation for adults 60 –74 and a universal recommendation for
adults ≥75 years would potentially highlight more clearly for providers and other public
health officials which adults are likely to benefit from an RSV vaccine and provide a
clearer recommendation for patients. Re-evaluating Shared Clinical Decision -Making (SCDM)
recommendation
9▪Dr. Iona Munjal (Pfizer)
▪Dr. Susan Gerber (GSK)
▪Dr. Rituparna Das (Moderna)
▪Dr. James Donahue (Marshfield Clinic Research Institute)
▪Dr. Patricia Lloyd (FDA)
▪Dr. Diya Surie (CDC, NCIRD)
▪Dr. David Hutton (University of Michigan)
▪Dr. David Hutton (University of Michigan)
▪Dr. Ismael Ortega -Sanchez (CDC/NCIRD)
▪Dr. Michael Melgar (CDC/NCIRD), Lauren
Roper (CDC/NCIRD), Dr. Amadea Britton (CDC/NCIRD)
▪Dr. Michael Melgar (CDC/NCIRD)Agenda: Wednesday June 26, 2024
▪Manufacturer presentation: ABRYSVO (Pfizer) safety and
immunogenicity in non -pregnant adults aged 18 -59 years
▪Manufacturer presentation: AREXVY (GSK) immunogenicity
with a 24 -month revaccination interval
▪Manufacturer presentation: mRESVIA  (Moderna) season 2
safety and efficacy update
▪Postmarketing  safety updates: Vaccine Safety Datalink
▪Evaluation of Guillain -Barre Syndrome (GBS) following RSV
vaccination among adults 65 years and older
▪Observational RSV vaccine effectiveness
▪Economic analysis of adult RSV vaccination
▪Update to benefits and risks discussion
▪Comparison of economic analyses of adult RSV vaccination
▪Evidence to Recommendations
▪Clinical Considerations
10
For more information, contact CDC
1-800 -CDC -INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

Summary: 1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD  Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP)  June 26, 2024…


02 RSV Adult Munjal 508

RSVpreF Adult Clinical
Development Update
ACIP Meeting 26 June 2024Iona Munjal, MD
2Extending Adult IndicationBivalent Stabilized Prefusion F
•Based on contemporary RSV A & RSV B strainsRSVpreF Adult Clinical Development Program Updates
ABRYSVO®
(Respiratory Syncytial Virus Vaccine)
•≥60 years (RENOIR trial) Season 2 analyses
•≥18 years at High Risk for RSV ( MONeT  trial)
•Real-world effectiveness dataAdditional Clinical Trial Data
Indication for ABRYSVO
Maternal
Immunize pregnant women
to prevent RSV -associated
lower respiratory tract
disease (LRTD) in infants
from birth through 6 months
of ageOlder Adult
Active immunization
to prevent
RSV-associated
LRTD in adults
≥ 60 years of ageApplication Submitted for FDA Review
Active immunization to prevent
RSV-associated LRTD in adults
18-59 years of age

3Updated Data on RENOIR, Real -World Evidence, and MONeTRSVpreF Adult – Clinical Development Program
•Revaccination
Y1 and Y2•Revaccination
Y3 and Y4•Adults 18 -59
with chronic
medical
conditions •Adults ≥ 18 with
immuno -
compromising
conditions Adults ≥ 60 Adults 18 –59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65RENOIR MONeT COVID COAD FLU COAD REAL -WORLDAdults ≥ 18 Older Adults ≥ 60
•Efficacy
through 2
seasonsAdults ≥ 60
•KPSC
Observational
Retrospective
Case Control
Study•Non-inferiority
demonstrated•Non-inferiority
demonstrated
Ongoing Ongoing Ongoing Ongoing
KPSC, Kaiser Permanente Southern California
4Unsolicited AEs
SAEs, NDCMCsLocal Reactions
Systemic EventsStart Season 1 (2021) End Season 1 Start Season 2 End Season 2 (2023)
TheRSV Vaccine Efficacy Study iNOlder Adults
Immunized Against RSV Disease
Study Start End of S1 Analysis
(Northern and Southern Hemisphere) Mid-Season 2 Analysis
(Northern Hemisphere)
Weekly active surveillance for acute respiratory symptomsePrimary Analysis End of S2 Analysis
(Northern and
Southern
Hemisphere)
16.4 months  7.1  months 7.6  monthsSafety
Surveillance
Average
Time Since
Vaccination Weekly active surveillance for acute respiratory symptomse
RSV, respiratory syncytial virus; RSVpreF, respiratory syncytial virus prefusion F subunit, AE, adverse event; NDCMC, newly d iagnosed chronic medical condition;
SAE, serious adverse event.38,863  participants / Adults  ≥60 years
5LRTD = lower respiratory tract disease
1. Eiras D. 2024 (May 17 -22). ATS  2. Walsh EE, et al. N. Engl J Med . 2023:338:1465 -1477.RSVPreF  Maintained High Efficacy in Season 2
VE Against RSV -associated LRTD in Subjects with ≥3 New or Worsened Lower Respiratory Symptoms (95% CI)1,2
40%50%60%70%80%90%100%
Season 1 Season 2 Across 2 SeasonsSeason 1 Season 20%88.9% (53.6, 98.7)
77.8% (51.4, 91.1)81.5% (63.3, 91.6)Primary endpoint:
RSV-LRTD with ≥3 symptoms
6.Consistent Efficacy was Observed Across RSV Overall and by
Subgroups A and B
RSV-LRTI with ≥ 3 SymptomsNumber of Events1Vaccine Efficacy
(95% CI) RSVPreF Placebo
OverallSeason 1 2 18 88.9% (53.6, 98.7)
Season 2 8 36 77.8% (51.4, 91.1)
Across 2 Seasons 10 54 81.5% (63.3, 91.6)
RSV-ASeason 1 1 5 80.0% (-78.7, 99.6)
Season 2 5 26 80.8% (49.1, 94.2)
Across 2 Seasons 6 31 80.6% (52.9, 93.4)
RSV-BSeason 1 1 12 91.7% (43.7, 99.8)
Season 2 2 10 80.0% (6.1, 97.9)
Across 2 Seasons 3 22 86.4%  (54.6, 97.4)
-20 0 20 40 60 80 100
Vaccine Efficacy (%, 95% CI)Primary endpoint:
RSV-LRTD with ≥3 symptoms
1. Represents LRTD (lower respiratory tract disease) events. One S1 case and one S2 case (both in the placebo group) and one S2 case in RSVPreF  group were based on local testing without RSV subgroup. One S2 case in placebo group had
both A and B subgroups;
Notes: RSV, respiratory syncytial virus; VE, vaccine efficacy
7Updated Data on RENOIR, Real -World Evidence, and MONeTRSVpreF Adult – Clinical Development Program
•Revaccination
Y1 and Y2•Revaccination
Y3 and Y4•Adults 18 -59
with chronic
medical
conditions •Adults ≥ 18 with
immuno -
compromising
conditions Adults ≥ 60 Adults 18 –59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65RENOIR MONeT COVID COAD FLU COAD REAL -WORLDAdults ≥ 18 Older Adults ≥ 60
•Efficacy
through 2
seasonsAdults ≥ 60
•KPSC
Observational
Retrospective
Case Control
Study•Non-inferiority
demonstrated•Non-inferiority
demonstrated
Ongoing Ongoing Ongoing Ongoing
8Abrysvo
Unvaccinated
Abrysvo
UnvaccinatedCASES
RSV +
CONTROLS
RSV -Study
Events
with Test
ResultsSOURCE POPULATION
Adults ≥60 years
Hospitalized or with
Emergency Department Visit
for Lower Respiratory Tract
Disease
•Large healthcare network  with high -risk population: Kaiser Permanente Southern California (KPSC)
•↑ RSV testing by salvaging NP/nasal swabs collected for other respiratory pathogen testing
•VE against RSV -related LRTD hospitalization/ED visits calculated using multivariable logistic regression
•Primary analysis controls: RSV -, hMPV -, influenza -, SARS -CoV-2-, and non -vaccine -preventable disease pathogen+
•Sensitivity analysis with all RSV negative as controlsLeveraging KPSC  High -quality Real -World Data PlatformKaiser Permanente Southern California Real -World Data: Observational
Retrospective Test Negative Design Case Control Vaccine Effectiveness Study
Figure adapted from: Fukushima et al  (2017) Basic principles of test -negative design in evaluating influenza vaccine effectiven ess
ARI, acute respiratory illness; ED, emergency department; hMPV, human metapneumovirus; LRTD  , lower respiratory tract disease; NP, nasopharyngeal; RSV, respiratory syncytial virus; VE, vaccine efficacy; VPD , vaccine preventable disease
9Early Real -World Data Reinforces VE among Persons at Highest Risk of Severe
RSV Disease: 89% -- Similar to Randomized Clinical Trial VE Results
a Pre-specified primary analysis controls test negative for RSV, flu and SARS -CoV2  and test positive for a non -vaccine preventable disease in the primary analysis. A sensitivity analysis includes a broader cont rol group definition which is all
who test negative for RSV. b Adjusted for age, sex, encounter months, race/ethnicity, Charlson  index, previous outpatient encounters, previous inpatient encounters, previous ED encounters, COPD, diabetes, renal disease, and peripheral
vascular disease. c Patient 1: 93 years old, Charlson  index of 6; Patient 2: 63 years old, Charlson  index of 4. Vaccine Effectiveness against RSV -related LRTD hospitalization or ED visit
Test Negative Controlsa
N (%)Test Positive Cases
N (%) Crude
VE (95%CI)Adjusted VEb
(95% CI) Unvaccinated,
n (%)Vaccinated,
n (%)Unvaccinated,
n (%)Vaccinated,
n (%)
Primary Analysisa
(n=1336)734 (96.6%) 26 (3.4%) 574 (99.7%) 2c(0.3%)90%
(58–98)89%
(52–97)
•Study population description
•57% of study population was over 75 years of age
•93% ≥1 Charlson  comorbidity
•14% immunocompromised
•Primary analysis VE= 89% (95% CI: 52 –97) (Table)
•Sensitivity Analysis (controls with any RSV negative) VE = 89% (95% CI: 54 –97)
•Study extension planned to provide Abrysvo VE for specific population subgroups (e.g., by age, high -risk conditions) and seasons  2, 3, and beyondResults
10Updated Data on RENOIR, Real -World Evidence, and MONeTRSVpreF Adult – Clinical Development Program
•Revaccination
Y1 and Y2•Revaccination
Y3 and Y4•Adults 18 -59
with chronic
medical
conditions •Adults ≥ 18 with
immuno -
compromising
conditions Adults ≥ 60 Adults 18 –59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65RENOIR MONeT COVID COAD FLU COAD REAL -WORLDAdults ≥ 18 Older Adults ≥ 60
•Efficacy
through 2
seasonsAdults ≥ 60
•KPSC
Observational
Retrospective
Case Control
Study•Non-inferiority
demonstrated•Non-inferiority
demonstrated
Ongoing Ongoing Ongoing Ongoing
11Licensure in 18 –59 Years of Age Will Be Based on Satisfactory Safety and Immunogenicity
Compared to RSVPreF  in Adults ≥ 60 YearsSafety in Adults 18 –59 Years Has Been Demonstrated in 7 Clinical Studies
Totality of Safety Data to Support Licensure in Adults ≥18 to 59 Years
] Study 1001 (n=98): Phase 1/2 Dose Ranging
Human Challenge  (n=35): Safety and Efficacy of 120μg without Adjuvant
Study 1014 (n=745): Lot Consistency
Study 1004 (n=282): Non-pregnant Concomitant Tdap
Study 1003 (n=115): Pregnant Women, Safety, Early Efficacy
Study 1008 (n=3689): Pregnant Women, Safety, Pivotal Efficacy
Study 1023 (n=453): (MONeT ) Immunogenicity & Safety1
>5,400 Adults Aged 18 -59 Years of Age 2
3
4
5
6
7

12Phase 3 Study Design MONeT   Substudy  A (Chronic Conditions)RSVPreF  in Adults ≥18 to 59 Years of Age at High Risk of
Severe RSV Disease
Adults ≥18 to 59 Years of Age  N = 675 Day 1 Month 1 Month 6
Vaccination 1 Follow -Up Follow -Up
Blood draw and vaccination Blood draw
Reactogenicity e -diary
AEs
AESIs, SAEs, NDCMCs
2:1RSVPreF 120 µg
Placebo
e
RENOIR Adults ≥60 Years of Age Pre-vaccination 1 Month Post -Vaccination
Bridged Immunogenicity
to RENOIRBlood draw Blood draw
 Historical cohort
1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File
13RSVPreF
120 µg
(N = 453) ;
n (%)Placebo
(N = 225) ;
n (%)Total
(N = 678) ;
n (%)
Sex
Male 193 (42.6) 73 (32.4) 266 (39.2)
Female 260 (57.4) 152 (67.6) 412 (60.8)
Race
White 312 (68.9) 152 (67.6) 464 (68.4)
Black or African American 106 (23.4) 57 (25.3) 163 (24.0)
Asian 24 (5.3) 9 (4.0) 33 (4.9)
Ethnicity
Hispanic/Latino 102 (22.5) 48 (21.3) 150 (22.1)
Non-Hispanic/non -Latino 348 (76.8) 175 (77.8) 523 (77.1)
Age at Vaccination
18-49 Years 240 (53.0) 113 (50.2) 353 (52.1)
50-59 Years 213 (47.0) 112 (49.8) 325 (47.9)
Mean (SD) 46.8 (9.9) 46.4 (10.5) 46.7 (10.1)
* Participants with multiple comorbidities are represented more than onceDemographics Between Vaccine and Placebo Recipients
RSVPreF
120 µg
(N = 453) ;
n (%)Placebo
(N = 225) ;
n (%)Total
(N = 678) ;
n (%)
With At Least 1 Prespecified
Medical Condition*453 (100.0) 223 (99.1) 676 (99.7)
Chronic Pulmonary
Conditions239 (52.8) 116 (51.6) 355 (52.4)
COPD 25 (5.5) 11 (4.9) 36 (5.3)
Asthma 198 (43.7) 88 (39.1) 286 (42.2)
Cardiovascular Conditions 38 (8.4) 16 (7.1) 54 (8.0)
CHF 9 (2.0) 3 (1.3) 12 (1.8)
CAD 19 (4.2) 4 (1.8) 23 (3.4)
Diabetes 189 (41.7) 101 (44.9) 290 (42.8)
Other 139 (30.7) 68 (30.2) 207 (30.5)
Liver Disease 20 (4.4) 13 (5.8) 33 (4.9)
Renal Disease 17 (3.8) 4 (1.8) 21 (3.1)
Neurologic Disease 16 (3.5) 1 (0.4) 17 (2.5)
Tobacco Use
Current Tobacco Use 78 (17.2) 39 (17.3) 117 (17.3)
1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File
14Local Reactions
Median Time to Resolution: 1 –2 days
36.6%
11.6%35.3%
10.7%
6.0%
0.4%7.1%
0.9%
0102030405060708090100
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
PlaceboPain at
Injection
Site1Redness2Swelling2Any
1. Severity definition: mild = no interference with daily activity; moderate = some
interference with daily activity; severe = prevents daily activity
2. Severity definition: mild = >2 -5 cm, moderate = >5 -10 cm; severe = >10 cm
RSVPreF N = 451; placebo N = 225Solicited Local/Systemic Reactions & Systemic Events Were
Mild to Moderate and Resolved Quickly in Participants 18 –59 Years
Systemic Events
Median Time to Resolution: 1 –2 days
1. Severity definition: mild = no interference with daily activity; moderate = some interference with daily activity; severe = prevents daily activity
2. Severity definition: mild = 2 -3 loose stools in 24h; moderate = 4 -5 loose stools in 24h; severe = 6 or more loose stools in 2 4h
3. Severity definition: mild 38.0 °C-38.4 °C; moderate >38.4 °C-38.9 °C; severe >38.9 °C-40.0 °C; grade 4 >40.0 °C
4. Severity definition: mild = 1 -2 time(s) in 24h; moderate = >2 times in 24h; severe = requires intravenous hydration
RSVPreF N = 451: Placebo N = 22557.4%55.6%
37.3% 38.2%
28.4%30.2%
24.4%
16.0% 14.9%16.9%
12.4%10.2%11.8%10.2%
2.0% 1.3% 1.6% 1.3%RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
Placebo
RSVpreF
120µg
PlaceboFatigue1Headache1Muscle
Pain1Any Joint Pain1Nausea1Vomiting4Diarrhea2Fever3
 Mild Moderate Severe
1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File
15*Related event was urticaria Grade 1 on the day of vaccination that resolved without treatment or medical attention;
Abbreviations: AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.Adverse Events Comparable Between Vaccine and Placebo Groups
Adverse Event CategoryRSVPreF 120 µg
(N = 453) ; n (%)Placebo
(N = 225) ; n (%)
From Vaccination Through 1 -Month Follow -Up Visit
Any Event 31 (6.8) 17 (7.6)
Related*1 (0.2) 0
Severe 1 (0.2) 4 (1.8)
From Vaccination Throughout the Study
SAE 5 (1.1) 7 (3.1)
Related SAE 0 0
AE Leading to Withdrawal 1 (0.2) 1 (0.4)
AE Leading to Death 1 (0.2) 0
AE of Special Interest
     (includes GBS and atrial fibrillation)0 0
1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File
16Seroresponse Rate RSV A & B (Comparison: 18 –59y High Risk to ≥60y) SRR Difference* (95% CI)
SRR Difference RSV -A 5.1 (1.2, 9.2)
SRR Difference RSV -B 8.3 (4.2,12.6)
Abbreviations: GMR = geometric mean ratio; SRR=seroresponse rate
*Analysis of covariance model used as per protocol with sex and baseline titer (in logarithm scale) adjustedNon-Inferiority Met for All Four Co -Primary Endpoints
GMR RSV A & B  (Comparison: 18 –59y High Risk to ≥60y) GMR (95% CI)
Model Adjusted* GMR RSV -A 1.57 (1.396, 1.759)
Model Adjusted* GMR RSV -B 1.52 (1.333, 1.725)
0.667 1.0 1.5 2.0
GMT Ratio
-10.0 0.0 10.0
SRR Differences (%)Both Primary Endpoints Met Non -inferiority (CI LB >0.667)
Both Primary Endpoints Met Non -inferiority (CI LB > -10%)
1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File
17RENOIR study has shown duration of protection is at least 2 years with high efficacy in season 2
RSVPreF  Addresses a Significant Burden in Adults and Those With Chronic ConditionsSummary of Clinical Development Updates of RSVPreF in Adults
RSVpreF in adults 18 –59 years of age ( MONeT  study) demonstrated robust RSV -A and RSV -B subgroup
neutralizing responses that met NI to the RENOIR study, where safety and efficacy were demonstrated
RSVPreF  is currently under review by the FDA for use in adults 18 -59 years of agePreliminary real -world observational data supports RCT efficacy in older population, largely with
comorbidities

Summary: RSVpreF Adult Clinical  Development Update ACIP Meeting 26 June 2024Iona Munjal, MD 2Extending Adult IndicationBivalent Stabilized Prefusion F •Based on contemporary RSV A & RSV B strainsRSVpreF Adult Clinical Development Program Updates ABRYSVO® (Respiratory Syncytial Virus Vaccine) •≥60 years (RENOIR trial) Season 2 analyses •≥18 years at High Risk for RSV ( MONeT  trial)  •Real-world effectiveness dataAdditional Clinical Trial Data Indication for ABRYSVO Maternal Immunize pregnant women  to…


03 RSV Adult Gerber 508

CO-1
AREXVY (Adjuvanted RSVPreF3)
2-Year Update
ACIP June 26, 2024
Susan Gerber, MD
Medical Director
GSK
Presentation by GSK at ACIP June 26, 2024
CO-2
AREXVY Indications
AREXVY now indicated for active immunization for prevention of lower
respiratory tract disease (LRTD) caused by RSV in
▪Individuals ≥ 60 YOA
▪Individuals 50-59 YOA at increased risk for LRTD caused by RSV
YOA: years of age
FDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed June 2024)
CO-3
Risk Factors for Severe RSV Disease Are Highly Prevalent Among
Adults ≥ 50 Years with Disparities Observed by Race and Ethnicity
▪31.4%  of adults 50–59 YOA and 46.9%  of adults ≥ 60 YOA are diagnosed with ≥ 1 risk factor for severe RSV diseasea
▪Mexican American/other Hispanic and NH Black adults have significantly higher prevalence of ≥ 1 diagnosed risk factor in
each of these age groups (vs. NH White adults)b
aSelf-reported diagnosis of the following conditions: CHF, CHD, stroke, angina pectoris, MI, COPD (COPD, emphysema, or current chro nic bronchitis), asthma (current), diabetes, liver disease (current), renal
disease. bOther  race/multi -racial results not presented.
*Statistically significant based on two -sided P < 0.05. P -values were calculated based on pairwise chi -square analysis on 2x2 ta bles using non -Hispanic White adults as the reference group.
Notes: Retrospective, cross -sectional analysis of pooled NHANES data spanning the period 2011 -March 2020 .Weighting to the United States population conducted in accordance with NHANES published
guidelines: https://wwwn.cdc.gov/nchs/nhanes/tutorials/weighting.aspx . CHD, coronary heart disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; MI, myocardial infar ction;
NH, Non -Hispanic; NHANES, National Health and Nutrition Examination Survey; YOA, years of age.Horn et al. NFID ACVR, May 8 -10, 2024  31.4%46.9%
29.9%44.9% 43.6%
34.1%*36.9%*
24.1%*50.4%*54.0%*
29.9%44.9%
34.1%*50.4%*
36.9%*54.0%*
24.1%*43.6%
0%20%40%60%
50-59 years ≥60 yearsPercentage of US adults with
≥1 diagnosed risk factor for
severe RSV disease
NH White Mexican American/other Hispanic NH Black NH Asian50–5 9 YOA ≥ 60 YOA% of
US adults with
 ≥ 1 diagnosed risk
factor for severe
RSV disease
CO-4
AReSVi -004: Immunogenicity, Safety, Reactogenicity and
Persistence of Single Dose of AREXVY Vaccine and
Different Revaccination Schedules in Adults ≥ 60 YOA
Randomized, open -label, multi -country study (NCT04732871)
Presentation by GSK at ACIP June 26, 2024
CO-5
AReSVi-004 Phase 3 Study Design1-3
Timepoint
HI only
(n≈215)D1 M13 M24 M25 M60
Presentation by GSK at ACIP June 26, 2024*RSV M24 revaccination: Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose at 24 months post Dose 1; **Primary endpoints: NAb
(neutralizing antibody) geometric mean titers (RSV-A and RSV-B) at Day 1 (pre-vaccination), D31, M6, and M12 post-dose 1; ***CMI response in terms of frequency of RSVPreF3-
specific CD4+ and/or CD8+ T-cells expressing > 2 activation markers; CMI, cell-mediated immunity; HI, humoral immunity; 1. Schwarz TF et al. 2023; 2. ClinicalTrials.gov.
NCT04732871; 3. GSK, 2024 https://www.gsk-studyregister.com/en/trial-details/?id=212496  (All URLs accessed June 2024)M12 M18 M30 M36 M37 M42 M48 M49 M54
HI + CMI
(n≈115)
HI + CMI
(n≈345)Safety
 (n≈645)
RSV 1 Dose
N≈330
RSV Annual
N≈9901st analysis 2nd analysis 3rd analysisAnalyses may be performed or
regrouped depending on data availabilityFinal End
of Study
analysis AREXVY
Blood sample for HI responses
Blood sample for CMI responses4th analysis
R
3:1:1Current analysis
Re-randomization 1:1 (N≈ 330)
HI only
(n≈215)HI + CMI
(n≈115)
RSV M24
Revaccination*
N≈330
All participants followed for safety
Primary objective: To evaluate humoral immune response following 1-dose primary schedule up to 12 months post-dose 1**
Key secondary objectives: To evaluate humoral and CMI *** responses following 1-dose primary schedule and re-vaccination doses, up to study end (M60);
safety and reactogenicity also assessedAReSVi -004
CO-6
Presentation by GSK at ACIP June 26, 2024AReSVi -004
GMT
(ED60)
[95%CI]
M
6M
12M
18M
24M
25M
13100010000
M
6M
12M
18M
24M
25M
13RSV Annual Revaccination RSV M24 Revaccination RSV 1 Dose
TimepointD
31D
1100010000
D
31D
1RSV-A Serum Neutralization Titers RSV-B Serum Neutralization TitersHigher RSV -A and RSV -B Neutralizing Antibody Titers
Observed After 24 Month Vaccination Interval
RSV Annual revaccination (N=250 -341): Participants receiving first dose (Dose 1) of AREXVY at Day 1, followed by revaccination d ose at 12 months post Dose 1 and at 24 months post Dose 1;
RSV M24 revaccination (N= 223 -319): Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose  at 24 months post Dose 1;
RSV 1 dose (N=281 -318): Participants receiving single dose (Dose 1) of AREXVY at Day 1; ED60: estimated dilution 60; GMT: geomet ric mean titer
CO-7
CD4+ T -Cell Responses Increased 1 -Month Post Each
Vaccination DoseAReSVi -004
Presentation by GSK at ACIP June 26, 2024RSVPreF3 CD4+
T-cells, /106 cells
0500100015002000
1 201 401 601 M
6M
12M
18M
24M
25M
13D
31D
1
TimepointRSV Annual Revaccination RSV M24 Revaccination RSV 1 Dose
RSV Annual  revaccination (N=216 -286): Participants receiving first dose (Dose 1) of AREXVY at Day 1, followed by revaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV
M24 revaccination (N=68 -94): Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose at 24 months post Dose 1; RSV  1 dose (N=83 -95):
Participants receiving single dose (Dose 1) of AREXVY at Day 1; CD4+ T -cells expressing ≥ 2 activation markers including ≥ 1 cytokine among CD40L, 4 -1BB, IL -2, TNF -α, IFN -γ, IL-13, IL -17
events/ 106 cells; (by intracellular staining)
CO-8
Lower Prevaccination  RSV-A NAb Titers  Associated with Higher
Seroresponse Rates (≥ 4 -Fold Increase) Following Revaccination
n/N 22 / 67 4 / 67 6 / 67 3 / 67
NAb baseline
GMT (ED60)193 – <1,304 1,304 – <2,381 2,381 – <4,078 4,078 – 123,535Participants with
≥ 4-fold increase
in RSV- A NAb
titers at
M13 vs M12
[95% CI]
29 / 55 23 / 56 10 / 56 7 / 56
283 – <1,000 1,000 – <1,849 1,849 – <3,736 3,736 – 38,8400%20%40%60%80%100%
0 1 2 3 432.8
(21.8, 45.4)
6.0
(1.7, 14.6)9.0
(3.4, 18.5) 4.5
(0.9, 12.5)RSV Annual Revaccination
1 2 3 4Participants with
≥ 4-fold increase
in RSV- A NAb
titers at
M25 vs M24
[95% CI]
0%20%40%60%80%100%
0 1 2 3 41 2 3 417.9
(8.9, 30.4) 12.5
(5.2, 24.1)41.1
(28.1, 55.0)52.7
(38.8, 66.3)
Quartile* Quartile*RSV M24 Revaccination
Presentation by GSK at ACIP June 26, 2024*Participants were grouped into quartiles depending on their baseline NAb titers: 1 = baseline NAb min–<1; 2 = baseline NAb 1–<2 (median); 3 = baseline NAb 2 (median) –<3;
4 = baseline NAb 3–4. Participants in the quartile 1 had the lowest pre -revaccination NAb and those in the quartile 4 had the highest; ED60, serum dilution inducing 60% inhibition in plaque -
forming units; GMT, geometric mean titer; NAb, neutralizing antibody; RSV Annual revaccination: Participants receiving the first dose (Dose 1) of Arexvy  at Day 1, followed by a
revaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV M24 revaccination: Participants receiving the f irst dose (Dose 1) of Arexvy  at Day 1 followed by a
revaccination dose at 24 months post Dose 1.AReSVi -004
CO-9
Lower Prevaccination  RSV-B NAb Titers  Associated with Higher
Seroresponse  Rates (≥ 4 -Fold Increase) Following Revaccination
Presentation by GSK at ACIP June 26, 2024*Participants were grouped into quartiles depending on their baseline NAb titers: 1 = baseline NAb min–<1; 2 = baseline NAb 1–<2 (median); 3 = baseline NAb 2 (median) –<3;
4 = baseline NAb 3–4. Participants in the quartile 1 had the lowest pre -revaccination NAb and those in the quartile 4 had the highest; ED60, serum dilution inducing 60% inhibition in plaque -
forming units; GMT, geometric mean titer; NAb, neutralizing antibody; RSV Annual revaccination: Participants receiving the first dose (Dose 1) of Arexvy  at Day 1, followed by a
revaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV M24 revaccination: Participants receiving the f irst dose (Dose 1) of Arexvy  at Day 1 followed by a
revaccination dose at 24 months post Dose 1.0%20%40%60%80%100%
0 1 2 3 41 2 3 40%20%40%60%80%100%
0 1 2 3 41 2 3 4
Quartile* Quartile*58.2
(44.1, 71.3)
37.5
(24.9, 51.5)
19.6
(10.2, 32.4)12.5
(5.2, 24.1)17.9
(9.6, 29.2)
7.5
(2.5, 16.6)4.5
(0.9, 12.5)3.0
(0.4, 10.4)RSV Annual Revaccination RSV M24 Revaccination
Participants with
≥ 4-fold increase
in RSV-B NAb
titers at
M13 vs M12
[95% CI]Participants with
≥ 4-fold increase
in RSV-B NAb
titers at
M25 vs M24
[95% CI]
n/N 12 / 67 5 / 67 3 / 67 2 / 67
NAb baseline
GMT (ED60)351 – <1,607 1,607 – <2,453 2,453 – <4,133 4,133 – 36,39132 / 55 21 / 56 11 / 56 7 / 56
271 – <1,190 1,190 – <2,122 2,122 – <3,845 3,845 – 26,385AReSVi -004
CO-10
Safety and Reactogenicity Profile in Individuals Revaccinated at
Month 24 Similar to First Dose
Solicited AEs reported within 4 days of each vaccine dose (exposed set)
AE, adverse event; M, month; RSV 24M revaccination: Participants receiving the first dose (Day 1 Dose) of RSVPreF3 OA investi gational vaccine at Day 1 followed by a revaccination
dose at 24 months (M24 Dose) post -Dose 1 (n=270 -328). Grade 3: >100 mm for erythema and swelling; significant pain at rest, prev ents normal everyday activities for pain; prevents
normal activity for headache, fatigue, myalgia, and arthralgia; >39.0 °C (102.2 °F) for fever.RSV M24 Revaccination
(Day 1 Dose)RSV M24 Revaccination
(M24 Dose)
020406080100
% of
Participants
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)
M24 Revac
(Day 1)
M24 Revac
(M24)Grade 3
11.6 11.461.3
56.1
10.17.714.917.830.535.2
1.5 1.921.326.332.6 31.1Arthralgia Fatigue Fever Headache Myalgia Erythema Pain Swelling
Unsolicited AEs, SAEs, Fatal SAEs and pIMDs  of individuals who were revaccinated at Month 24 are also similar to those vaccinated at Day 1Local SystemicAReSVi -004
CO-11
AReSVi -004 Summary
Revaccination at a 24 -month interval provides higher RSV -A and RSV -B neutralizing antibody
titers as compared to a 12 -month interval 1
Safety and reactogenicity profiles of second dose comparable with first dose 3
The l ower  the prevaccination  RSV-A and RSV -B neutralizing antibody titers  observed at 2 years
post initial vaccination, the higher the seroresponse  rates after  revaccination 2
Presentation by GSK at ACIP June 26, 2024
Future results from this trial will help inform optimal revaccination timing 4
CO-12
Postmarketing  Safety Update
Presentation by GSK at ACIP June 26, 2024
CO-13
AREXVY: Post -Licensure Safety Surveillance  After 1 Year
Reflects Acceptable Safety Profile in Clinical Trials
Presentation by GSK at ACIP June 26, 2024*IQVIA NPA Rapid Weekly TRx, to 13 May 2024
**Based on GSK safety database, spontaneous AE reports not necessarily causally -related to vaccination
1. Sejvar  JJ, et al. 2011; AE: adverse event ; VSD: vaccine safety datalink; BEST: biologics effectiveness and safety
▪1,640 AE reports received (launch 3 May ’23 -2 May ‘24)**
▪82% from US
▪89% non -serious
▪Since launch, GSK received 12 reports of GBS, all from US
▪Observed vs expected, based on 7,246,910 AREXVY doses administered
in US and background incidence rate = 2.1 / 100,000 PY3
Vaccine
Exposure▪~ 8 million  doses  of AREXVY administered in US since launch*
AE▪1,640 AEs (from US, 1,344 AE reports received) [launch 3 May ’23 -2 June ’24]**
▪89% non -serious
▪Majority related to labelled reactions
GBS▪Since launch, GSK received 13 reports of GBS, all from US
▪Reports do not exceed expected background incidence1
▪17 cases expected in absence of vaccination
▪VSD and BEST initiative will provide additional assessment of GBS
CO-14
Overview of Clinical Development Program
Presentation by GSK at ACIP June 26, 2024
CO-15
AREXVY Clinical Development Program
AReSVi -004 study
Older adults ≥60 YOA
Safety, reactogenicity, immunogenicity, persistence, and re -vaccination
RSV OA=ADJ -019 study
Older adults ≥60 YOA
Safety, reactogenicity, immunogenicity when
co-administered with PCV20
RSV OA=ADJ -020 study
Older adults ≥50 YOA
Safety, reactogenicity, immunogenicity when
co-administered with HZ/ su vaccine
Phase 2b
Phase 3
Completed
Ongoing/
in progress
RSV OA=ADJ -025 study
Adults 18 –49 years of age compared
to older adults ≥60 years of age
Safety and immunogenicity
RSV OA=ADJ -007,
RSV OA=ADJ -017, RSV OA=ADJ -008
Safety, reactogenicity, immunogenicity when
co-administered with FLU -QIV, FLU -aQIV ,
FLU-QIV-HD, respectively
RSV OA=ADJ -013 study
Older adults ≥50 YOA
Safety, reactogenicity, immunogenicity when
co-administered with COVID -19 mRNA
vaccine
Presentation by GSK at ACIP June 26, 2024FLU-aQIV : adjuvanted quadrivalent influenza vaccine; FLU -QIV: quadrivalent influenza vaccine; FLU -QIV-HD: high -dose quadrivalent influen za vaccine; HZ/ su: herpes zoster recombinant
subunit; 1MPD1: 1 month post dose 1; PCV20: 20 -valent pneumococcal conjugate vaccine; YOA: years of age
All studies ClinicalTrials.gov; All URLs accessed June 2024AReSVi -006 study
Older adults ≥60 YOA
Pivotal efficacy study
RSV OA=ADJ -018 study
Adults 50−59 YOA (incl. adults at
increased risk of RSV -LRTD) vs ≥60 YOA
Safety, reactogenicity, immunogenicity
RSV OA=ADJ -023 study
Immunocompromised adults ≥18 YOA
(lung and renal transplant recipients)
Safety and immunogenicity

CO-16
AREXVY (Single dose)AREXVY Placebo% VE (95% CI)
W/ season
covariateW/o season
covariateNumber of events (n/N)
RSV-LRTD 32 / 12,468 154 / 12,498 67.7%  (52.3, 78.7) 73.3%  (60.7, 82.4)
≥ 1 comorbidity of interest* 17 / 5,000 79 / 4,942 67.1%  (43.6, 81.8) 73.1% (54.2, 85.1)
≥ 70 years of age 12 / 5,506 74 / 5,517 74.6% (52.6, 87.5) 79.1% (61.3, 89.7)
Pre-frail** 9 / 4,794 50 / 4,779 71.3% (40.6, 87.7) 77.0% (52.7, 90.1)
Severe RSV-LRTD 9 / 12,468 54 / 12,498 74.9%  (48.4, 89.2) 78.6% (56.3, 90.7)
Vaccine Efficacy0% 20% 40% 60% 80% 100%Efficacy of a Single Dose of AREXVY over 2 Calendar Years
Presentation by GSK at ACIP June 26, 2024
Median follow-up: 23.3 monthsAReSVi -006
*Comorbidities of interest: COPD, asthma, any chronic respiratory or pulmonary disease, heart failure (cardiorespiratory cond ition), diabetes mellitus type 1 or 2, advanced liver or renal
disease (endocrine or metabolic condition); **frailty assessed using gait speed test: walking speed < 0.4 m/s or not able to perform test (frail), walking speed 0.4 –0.99 m/s
(pre-frail), walking speed ≥1 m/s (fit); Due to too few cases observed, cannot conclude VE  for frail and ≥ 80 years of age
CO-17
Conclusion
▪Immunogenicity data supports potential for revaccination with AREXVY
▪Stronger immune responses were observed in those revaccinated after
24-month interval compared to those revaccinated annually
▪Results from ongoing Phase 3 studies will help inform timing of
revaccination
▪AREXVY provides protection over 2 calendar years
▪Acceptable safety profile following administration of ~ 8 million doses
▪FDA recently expanded AREXVY’s indication to include use in individuals
50–59 YOA at increased risk for RSV-LRTD
▪Will help to close equity gap by broadening access for populations at
increased risk for severe disease caused by RSV
CO-18
AREXVY (Adjuvanted RSVPreF3)
2-Year Update
ACIP June 26, 2024
Susan Gerber, MD
Medical Director
Presentation by GSK at ACIP June 26, 2024

Summary: CO-1 AREXVY (Adjuvanted RSVPreF3)  2-Year Update ACIP June 26, 2024 Susan Gerber, MD Medical Director  GSK Presentation by GSK at ACIP June 26, 2024 CO-2 AREXVY Indications  AREXVY now indicated for active immunization for prevention of lower  respiratory tract disease (LRTD) caused by RSV in ▪Individuals ≥ 60 YOA ▪Individuals 50-59 YOA at increased risk for LRTD caused by RSV YOA: years of age FDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL…


04 RSV Adult Das 508

1
Update on Moderna’s RSV Vaccine,
mRESVIA (mRNA -1345), in Adults
≥60 Years of Age
Advisory Committee on Immunization Practices (ACIP)
Rituparna Das, MD PhD
June 26, 2024
2
Licensure of mRESVIA, Moderna’s RSV Vaccine
(mRNA -1345) in United States
▪FDA approval obtained May 31, 2024
▪Indication/Presentation
▪For active immunization for the prevention of lower respiratory
tract disease (LRTD) caused by respiratory syncytial virus (RSV)
in adults 60 years of age and older
▪Single dose regimen
▪Prefilled syringe
3
Outline of
Presentation▪Pivotal Phase 2/3 Trial
▪Brief review of study design
▪Update on safety
▪Update on efficacy
▪12-month revaccination data
▪Safety
▪Immunogenicity
▪Summary
4
Pivotal Safety and Efficacy Study Design
Population
▪Healthy adults including those with chronic, stable medical conditions, and/or frailty
▪≥ 60 years of age
▪22 countries (both Northern and Southern Hemisphere)
Regimen and follow -up
▪Single -dose regimen (1:1 50 μg RSV vaccine or saline placebo)
▪24-month follow -up
Stratified by
▪Age (60 - 74 and ≥ 75 years)
▪Presence or absence of congestive  heart failure or chronic  obstructive pulmonary
diseaseStudy 301
clinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434
Wilson et al NEJM , 2023.
5
▪RSV efficacy study
conducted across 3
seasons
▪>50% of participants
enrolled in US
▪Primary Analysis:
Met success criteria
▪Additional Analysis:
>90% of participants
followed for ≥ 6 months
▪March 2024 Analysis:
>90% of participants
followed for ≥12 monthsTrial Analyses
US 2021 -2023 RSV Hospitalization Rates (RSV -NET) in Adults ≥ 65 Years1
Overall RSV
Hospitalization
Rate per
100,000 Adults
≥ 65 Years1
012345678910
2021 -2022
RSV SeasonAdditional Analysis
November 2021 – April 2023
Median 8.6 Months (range 0.5 – 17.7)
Follow -upVaccination Period
November 2021 – December 2022
Primary Analysis
November 2021 – November 2022
Median 3.7 Months (range 0.5 - 12.6)
Follow -up
2022 -2023
RSV SeasonMarch 2024 Analysis
November 2021 – March 2024
Median 18.8 Months (range 0.5 – 24)
Follow -up
1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -impacted -hospitalizations.html 2023 -2024
RSV Season
2021 2022 2023 2024
6
Timing of Vaccination and RSV Surveillance
Vaccination
▪COVID -19 pandemic precluded the assumption of standard RSV seasons
▪Subjects vaccinated year -round for ~ 1 year (not limited to pre -RSV season)
Surveillance
▪Active surveillance of >36,000 participants for RSV year -round (not limited to RSV seasons)
▪Included 2022/2023 and 2023/2024 high incidence RSV seasons1
▪Background rates in placebo recipients, 14 days - 24 months:
▪RSV-LRTD with ≥ 2 symptoms: 9.3 cases/1000 person years
▪RSV-LRTD with ≥ 3 symptoms: 3.7 cases/1000 person years
▪RSV-ARD: 16.4 cases/1000 person years
▪683 confirmed RSV -ARD cases reported over 24 months  Study 301
clinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434
1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -impacted -hospitalizations.html
7
Demographics of Study Participants
CharacteristicRSV Vaccine (mRNA -1345)
(N = 18,427)Placebo
(N = 18,387)
Median Age, years 67 67
Male, n (%) 9,410 ( 51%) 9,330 (51%)
Age Group, n (%)
60 – 69 Years 11,437 (62%) 11,399 (62%)
70 – 79 Years 5,546 (30%) 5,534 (30%)
≥ 80 Years 1,444 (8%) 1,454 (8%)
Race/Ethnicity, n (%)
White 11,311 (61%) 11,290 (61%)
Black or African American 2,204 (12%) 2,173 (12%)
Asian 2,151 (12%) 2,138 (12%)
Hispanic / Latino Ethnicity 6,117 (33%) 6,168 (34%)
Frailty Status ( ≥4 on Edmonton frail score)  3,862  (21%) 3,946 (21%)Study 301
Age, gender, race/ethnicity, and frailty status balanced between vaccine and placebo recipients
Race/ethnicity generally representative of US populationRandomization Set
March 8, 2024 data cutoff
8
Prespecified Comorbidities among Study Population
RSV Vaccine (mRNA -1345)
(N = 18,427)Placebo
(N = 18,387)
 ≥1 Prespecified Comorbidity  (%) 5,463 (30%) 5,357 (29%)
Chronic obstructive pulmonary disease (COPD) 1,097 (6%) 1,112 (6%)
Asthma 1,410 (8%) 1,365 (7%)
Chronic Respiratory Disease189 (0.5%) 84 (0.5%)
Diabetes 3,292 (18%) 3,207 (17%)
Congestive Heart Failure (CHF) 276 (2%) 268 (2%)
Advanced Liver Disease 49 (0.3%) 44 (0.2%)
Advanced Renal Disease 111 (0.6%) 127 (0.7%)Study 301 – Randomization Set
•~30% of study participants with comorbidities
•Comorbidities balanced between vaccine and placebo recipients
1. Chronic respiratory disease includes chronic pulmonary fibrosis (idiopathic and otherwise), restrictive lung disease, asbe stosis, bronchiectasis, cystic fibrosis,
pulmonary hypertension, sarcoidosis, and history of tuberculosis
March 8, 2024 data cutoffRandomization Set
9
Safety Data
Study 301
Safety Set – March 8, 2024 data cutoff
Based on median of 18.8 months of follow -up
10Unsolicited Adverse Events Within 28 Days After Injection,
Regardless of Relationship  to Vaccine/Placebo
RSV Vaccine (mRNA -1345)
(N = 18,369)Placebo
(N = 18,316)
 All, n (%) 3,823 (21%) 3,467 (19%)
Serious 126 (0.7%) 114(0.6%)
Fatal 2(<0.1%) 6 (<0.1%)
Medically -Attended 1,664 (9%) 1,587 (9%)
Leading to Study Discontinuation 2(<0.1%) 11(<0.1%)
Severe/ ≥ Grade 3 138(0.8%) 138(0.8%)
Non-Serious 3,697 (20%) 3,353 (18%)
Any Adverse Event of Special Interest  (AESI) 3(<0.1%) 9(<0.1%)Study 301
No imbalances in any categories between vaccine and placebo recipientsSafety Set
March 8, 2024 data cutoff
11
Adverse Events of Special Interest (AESI)
▪Neurological Disorders
▪No cases of acute disseminated encephalomyelitis (ADEM)
▪No safety concern with Guillain -Barre syndrome (3 unrelated cases reported >500 days
postinjection [1 vaccine, 2 placebo])
▪No imbalance observed for other neurological disorders including Bell’s palsy/facial
paralysis
▪Cardiac Events
▪No imbalance observed in cardiac arrhythmias such as atrial fibrillation
▪No confirmed cases of:
▪Acute myocarditis in vaccine recipients
▪Acute pericarditis in vaccine recipients with onset < 42 daysStudy 301
Safety Set
March 8, 2024 data cutoff
12
Efficacy Analyses
Study 301
13
Efficacy of mRNA -1345 Against RSV LRTD among Adults ≥ 60 Years
Cases, n (%)Primary Analysis (Case Driven)1
3.7 Months Median (range 0.5 - 12.6) Follow -up Additional Analysis1
8.6 Months Median (range 0.4 – 17.7) Follow -up
RSV Vaccine
(mRNA -1345)
(N = 17,561)Placebo
(N = 17,503)Vaccine
Efficacy
(%CI*)RSV Vaccine
(mRNA -1345)
(N = 18,074)Placebo
(N = 18,010)Vaccine
Efficacy
(% CI*)
RSV LRTD
≥ 2 symptoms15 (0.09%) 70 (0.40%)78.7%
(62.8%, 87.9%)48 (0.27%) 127 (0.71%)62.5%
(47.7%, 73.1%)
RSV LRTD
≥ 3 symptoms5 (0.03%) 26 (0.15%)80.9%
(50.1%, 92.7%)20 (0.11%) 51 (0.28%)61.1%
(34.7%, 76.8%)Study 301 – Primary and Additional Analyses
▪Vaccine protection continued through a high incidence RSV season (2022/2023)
▪Lower bound of confidence interval continued to exceed 20%Per Protocol Analysis
1.US product insert mRESVIA
* For primary analysis, the alpha -adjusted 95.04% CI and 95.10% CI for RSV LRTD ≥ 2 symptoms and ≥ 3 symptoms are presented, res pectively.
  For additional analysis, 95% CIs are presented.
  Efficacy based on hazard ratios
14Efficacy of mRNA -1345 Against RSV LRTD among Adults ≥ 60 Years -
18 Month Analysis
Study 301 - Per Protocol Set
▪Vaccine protection continued over a longer period through high incidence 2022/2023 and 2023/2024 RSV
seasons
▪Lower bound of the confidence interval continued to exceed 20%Cases, n (%)
RSV Vaccine
(mRNA -1345)
(N = 18,181)Placebo
(N = 18,132)Vaccine Efficacy (%)
(95% CI)
RSV LRTD
≥ 2 symptoms113 (0.6%) 225 (1.2%)50.3%
(37.5%, 60.7%)
RSV LRTD
≥ 3 symptoms46 (0.3%) 91 (0.5%)49.9%
(27.8%, 65.6% )March 2024  Analysis
March 8, 2024 data cutoff
 Efficacy based on incidence rates adjusted for person -time.
15Efficacy of mRNA -1345 by Age, Comorbidities, and Frailty
Against RSV LRTD ≥ 2 Symptoms
Study 301 - Per-Protocol Efficacy Set through 24 Months
▪Case splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty through 24 monthsNumbers of Events
RSV LRTD with ≥ 2 Symptoms RSV Vaccine
(mRNA -1345)
(N = 18,181)Placebo
(N = 18,132)Vaccine Efficacy
(95% CI)
Overall 132/18,181 248/18,132 47.4% (35.0, 57.4)
Age60 – 69 Years 83/11,269 147/11,238 44.3%  (27.1, 57.4)
70 – 79 Years 36/5,487 81/5,459 56.0%  (34.9, 70.3)
≥ 80 Years 13/1,425 20/1,435 35.3% (-30.1, 67.8)
ComorbiditiesNo Comorbidities 99/12,788 160/12,856 38.6%  (21.1, 52.2)
≥ 1 Comorbidities 33/5393 88/5276 63.4%  (45.4, 75.5)
Frailty StatusFit (0-3) 106/13,491 197/13,366 47.2%  (33.1, 58.3)
Vulnerable/Frail (≥ 4) 20/3802 39/3872 48.0%  (10.9, 69.7)
-40 -20 0 20 40 60 80 100
Vaccine Efficacy, % (95% CIs)
Comorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal diseas e
March 8, 2024 data cutoff
16
Efficacy of mRNA -1345 Against Severe LRTD Among Adults ≥ 60 Years
Study 301 - Post Hoc Analysis/Per Protocol Set
1.Falsey et al NEJM, 2005; 2. Panozzo et al ESWI, 2023▪Shortness of breath is a key driver of seeking a higher level of care1,2
▪Vaccine is efficacious in preventing shortness of breath associated with RSV -LRTD
▪Too few hospitalizations to assess vaccine efficacyVaccine Efficacy (95% CI)
Primary Analysis
3.7 Months Median
(0.5 - 12.6) Follow -up Additional Analysis
8.6 Months Median
(0.4 – 17.7) Follow -upMarch 2024 Analysis,
18 Month
RSV-LRTD Associated
Shortness of Breath1,286.7%
(41.9%, 97.0%)74.6%
(50.7%, 86.9%)56.7%
(33.1%, 72.6%)
17Efficacy of mRNA -1345 Against RSV LRTD with ≥ 2 Symptoms
Among Adults ≥ 60 Years Over Time
Study 301 – Post Hoc Analysis
~2.4%/month
decrease
Months Following VaccinationVaccine
Efficacy
(%)
20406080100
2 4 6 8 10 12 14 16 18
Weighted least square regression line and 95% CI (blue area) based on the bi -monthly VEs calculated using incidence rates adjust ing person time
over two -month periods
18
Persistence of RSV Antibody and Revaccination
at 12 Months
Study 302
19
Vaccination Regimen
Study 302, Parts B & C
NDay 1 12 Months
RSV Vaccine
(mRNA -1345) Placebo 254
RSV Vaccine
(mRNA -1345)
RSV Vaccine
(mRNA -1345)COVID -19
Bivalent Vaccine289Study 302, Part B Study 302, Part C
Participants from Study 302, Part B, were enrolled in Part C and revaccinated with RSV vaccine at 12 months
20Safety Events of Interest – Revaccination at 12 Months
with mRNA -1345
▪No reports of:
▪Deaths, SAEs, or AESIs as assessed as related by the
investigator
▪Anaphylaxis
▪Guillain Barre Syndrome
▪Acute disseminated encephalomyelitis (ADEM)
▪Bell’s palsy/facial paralysis
▪Acute myocarditis or acute pericarditisStudy 302 C  – Based on 2 Months Follow -up
Safety Set
SAE –serious adverse event; AESI –adverse event of special interest
Dec 4, 2023 data cutoff
21Durability of Neutralizing Antibody Responses Following Primary Dose and
Revaccination at 12 Months with mRNA -1345
Study 302C – Adults ≥50 Years
214818283
455419662
100100010000100000
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14RSV-A Neutralizing Antibody
GMT
Part C
12 Month RevaccinationPart B
Dose 1
GMR of
revaccination vs
first dose:
▪ RSV-A - 1.08
(0.99, 1.17)
▪RSV-B - 0.91
(0.84, 0.99)
Non-inferiority
criteria met (LB of
95% CI of GMR >
0.667) for RSV -A
and RSV -BGMFR from Day 0 8.5 9.2
▪RSV-A and RSV -B neutralizing antibodies detectable at 12 months post -vaccination
▪Revaccination with mRNA -1345 as soon as 1 year after primary vaccination elicits responses similar to that following
primary vaccination
▪Revaccination met pre -specified non -inferiority success criteriaStudy Month2.1
22
SUMMARY
23
RSV Vaccine (mRNA -1345)
▪Vaccine generally well tolerated in >19,700 adults ≥ 60 years  vaccinated with 50 g
licensed dose
▪No ADEM, no vaccine -related cases of GBS, or other safety concerns
Safety
▪Efficacious through median of ~19 months follow -up
▪Comparable efficacy in individuals ≥ 80-year-olds, with ≥ 1 comorbidity, and frail
▪Shown to prevent severe RSV disease based on analysis of shortness of breath

Efficacy
▪Strong humoral and cellular immune responses1 (ACIP Feb 2024)
▪Neutralizing antibody detectable through 12 months post -vaccination
▪Revaccination with mRNA -1345 as soon as 1 year after primary vaccination elicits
responses similar to that following primary vaccination
▪Revaccination well tolerated; no safety concerns
Immunogenicity/
Revaccination
▪Pre-specified immunogenicity criteria met & and no new safety concerns observed with
concomitant administration of mRNA -1345 with standard influenza & COVID -19 vaccines
(ACIP Feb 2024)
Concomitant
AdministrationSummary
1 Goswami et al, JID, 2024
24
THANK YOU!
24▪Investigators
▪Study site personnel
▪Laboratory personnel
▪Most importantly, the individuals who
participated in these trials

Summary: 1 Update on Moderna’s RSV Vaccine,  mRESVIA (mRNA -1345), in Adults  ≥60 Years of Age Advisory Committee on Immunization Practices (ACIP) Rituparna Das, MD PhD June 26, 2024 2 Licensure of mRESVIA, Moderna’s RSV Vaccine  (mRNA -1345) in United States  ▪FDA approval obtained May 31, 2024 ▪Indication/Presentation ▪For active immunization for the prevention of lower respiratory  tract disease (LRTD) caused by respiratory syncytial virus (RSV)  in adults 60 years of age and older ▪Single dose…


05 RSV Adult Donahue 508

Update: Rapid Cycle Analysis of RSV
Vaccines in Older Adults
Jim Donahue, PhD DVM
Marshfield Clinic Research Institute
Presented to the ACIP
June 26, 2024
1
RSV RCA Interim Report – June 26, 2024
•Description of Vaccine Safety Datalink and RCA
•Review of surveillance methods
•Descriptive analysis
•Sequential analysis
̶Immune thrombocytopenia (ITP)
̶Guillain -Barré syndrome (GBS)
̶Atrial fibrillation
2
Vaccine Safety Datalink 2024
*
3•Collaborative project between CDC and 13 integrated healthcare organizations
•Data on ~13.5 million persons per year
•Conducts rigorous vaccine safety studies and near -real-time monitoring
VSD Rapid Cycle Analyses (RCA)
4•Permits rapid assessment of vaccine safety
-Near real -time data for weekly, biweekly, or monthly analyses
•Outcome incidence in vaccinated persons compared to outcomes
incidence in a comparator group
-Outcomes are pre -specified
•Sequential analytic methods used to detect ‘statistical signals’
while maintaining a pre -defined type I error rate
-Type I error = mistakenly reject the null hypothesis (“false positive”)
•Statistical signals are interpreted as potential  associations
Objectives for RSV RCA in Older Adults
5•Monitor RSV vaccine uptake
•Monitor the occurrence of pre -specified outcomes following RSV
vaccination
•Conduct near real -time surveillance of pre -specified outcomes
using RCA methods
Study Design and Population
6•Near real -time surveillance among a prospective cohort of
persons ≥60 years old who received an RSV vaccine
•Member of a participating VSD infrastructure site
•Data are extracted every week and analyses are biweekly
•Surveillance period: 8/1/2023 through 5/31/2025
-Sequential analyses started in March 2024
•Project ends September 2025
Sequential Analysis Methods
7•Biweekly analysis includes a sequential test of the one -sided null
hypothesis that the vaccine does not increase the risk in the risk interval
•A ‘statistical signal’ occurs when the analysis produces a one -sided P value
that is less than a pre -specified threshold
•The signal threshold is determined from an alpha -spending plan that keeps
the overall chance of a Type 1 error <0.05 during the surveillance period
•Formal sequential analysis stops after a signal, but surveillance continues
•Design and analysis is analogous to that used in the VSD RCA of COVID -19
vaccines (Klein N, et al. JAMA 2021; 326:1390 –9)
Risk and Comparison Intervals
8•Primary risk interval for all outcomes will be 1 -21 days following
RSV vaccination except anaphylaxis and CIDP*
-Primary comparison interval of 43 -63 days
-Secondary comparison interval of 22 -42 days
•Secondary risk interval of 1 -42 days
-Comparison interval of 43 -84 days
•Anaphylaxis and CIDP will be descriptively monitored only
-Anaphylaxis (0 -1 days after RSV vaccination)
-CIDP (1 -84 days after RSV vaccination)
*chronic inflammatory demyelinating polyneuropathy
Analysis with Vaccinated Concurrent Comparators
9•Comparators are RSV vaccinees, who on the same day  as the exposed case
in a risk interval, were in the same stratum (e.g., age, sex, race/ethnicity,
VSD site), but in a comparison interval
•Outcome incidence is calculated during the risk interval and compared
with incidence in the comparison interval
-Relative risk estimates are computed with nominal 95% confidence intervals
-Adjusted for calendar day, age group, sex, race/ethnicity, VSD site
•Advantages of vaccinated concurrent comparators compared to
unvaccinated or historical comparators
-Permits adjustment for potential biases due to calendar time, site, and demographic
factors
-Less confounding by indication (e.g., persons with chronic illness more likely to seek
RSV vaccination and may be at increased risk of atrial fibrillation)
10RSV vaccinated
May 30th
RSV vaccinated
April 19th June 3rdJune 3rd1 21
43 63On each calendar day that an outcome occurs in a
vaccinee (e.g., June 3rd ), we compare vaccinees in
their risk interval (1 -21 days) with similar vaccinees
in their comparison interval (43 -63 days).
‘Similar’ means that people were in the same age
group, sex, race/ethnicity, and VSD site.
Inherently adjusts for calendar time.Risk interval 1 -21 days post -vaccination
Comparison interval 43 -63 days post -vaccination
Ref: Klein N, et al. Kaiser Permanente Northern CaliforniaVaccinated Concurrent Comparator Design
Four Exposure Groups
11GSK with simultaneous vaccination of another vaccine*
GSK without simultaneous vaccination
Pfizer with simultaneous vaccination of another vaccine*
Pfizer without simultaneous vaccination
*Non -RSV vaccines typically include routine, age -appropriate vaccines such as
COVID -19, influenza, RZV, PCV20/15, PPSV23,  Td/Tdap
Pre-specified Outcomes (n=14)
12Outcome Setting1Primary risk
interval (days)2
Acute disseminated encephalomyelitis (ADEM)3E, I 1-21
Acute myocardial infarction (AMI) E, I 1-21
Anaphylaxis3 E, I 0-1
Atrial fibrillation E, I, O, T 1-21
Bell’s palsy E, I, O, T 1-21
Chronic inflammatory demyelinating polyneuropathy (CIDP)3 E, I, O, T 1-84
Deep vein thrombosis (DVT) E, I, O, T 1-21
Encephalitis / myelitis / encephalomyelitis (not ADEM or TM) E, I 1-21
Guillain -Barré syndrome (GBS)3 E, I 1-21
Immune thrombocytopenia (ITP) E, I, O, T 1-21
Myocarditis / pericarditis E, I 1-21
Pulmonary embolism (PE) E, I 1-21
Stroke E, I 1-21
Transverse myelitis (TM)3 E, I 1-21
1E=Emergency department; I=Inpatient; O=Outpatient; T=Telehealth
2All outcomes also have a secondary risk interval of 1 -42 days after vaccination, except anaphylaxis and CIDP , which are descript ively monitored only .
3Chart review regardless of whether there is a statistical signal; sequential analyses will use only chart -confirmed cases (ADEM, GBS, and TM).
RSV Vaccines Administered in VSD,
8/1/2023 –5/25/2024
13•NOTE: All subsequent analyses and slides exclude RSV vaccines in the
‘Unspecified’ manufacturer categoryGSK Pfizer UnspecTotal
N % N % N %
338,290 87.7 47,287 12.3 152 0.0 385,729
14050001000015000200002500030000
07-30-23
08-06-23
08-13-23
08-20-23
08-27-23
09-03-23
09-10-23
09-17-23
09-24-23
10-01-23
10-08-23
10-15-23
10-22-23
10-29-23
11-05-23
11-12-23
11-19-23
11-26-23
12-03-23
12-10-23
12-17-23
12-24-23
12-31-23
01-07-24
01-14-24
01-21-24
01-28-24
02-04-24
02-11-24
02-18-24
02-25-24
03-03-24
03-10-24
03-17-24
03-24-24
03-31-24
04-07-24
04-14-24
04-21-24
04-28-24
05-05-24
05-12-24
05-19-24Vaccines RSV Vaccinations by Manufacturer and Week of
Administration
GSK
Pfizer
Total
WeekStart of
sequential
analysis
Results of Sequential Analysis
Six runs —data through 5/25/2024
15
VSD Outcomes Setting1Signal
(Y/N)
Acute disseminated encephalomyelitis (ADEM) E, I N
Acute myocardial infarction (AMI) E, I N
Atrial fibrillation (AF) E, I, O, T N
Bell’s palsy (BP)   E, I, O, T N
Deep vein thrombosis (DVT) E, I N
Encephalitis / myelitis / encephalomyelitis (ENCEPH) E, I N
Guillain -Barré syndrome (GBS) E, I N
Immune thrombocytopenia (ITP) E, I, O, T Y
Myocarditis / pericarditis ( MYOC ) E, I N
Stroke (STK) E, I N
Transverse myelitis (TM) E, I N
Pulmonary embolism (PE) E, I N16RSV RCA Vaccine Statistical Signals in VSD (5/25/2024)
1E = ED, I = Inpatient, O = Outpatient, T=Telehealth
Analysis Parameters Signal Information and Informative Counts Nominal AnalysisSequential
Test
Outcome
EventRisk
Interval
DaysComp
Interval
DaysVaccine
TypeSignaled
in a
Prior
Run1New
Sequential
Analysis
Signal2Events
in Risk
IntervalEvents in
Comp
IntervalAdjusted
Expected
Events in
Risk
IntervalAdjusted
Rate
Ratio395%
Confidence
Interval42-sided
P Value1-sided
P Value5
ITP 1-21 43-63 GSK w simul n/a No 2 1 0.6 3.08 0.23-92.44 0.408 0.347
GSK wo simul n/a No 19 8 8.1 2.35 0.99-5.97 0.054 0.040
Pfizer w simul n/a No 0 1 0.2 0.00 0.00-81.18 0.810 0.810
Pfizer wo simul n/a No 2 2 1.8 1.10 0.11-11.27 0.931 0.659
22-42 GSK w simul n/a No 3 2 1.4 2.21 0.31-19.61 0.432 0.340
GSK wo simul n/a Yes 19 6 6.3 3.04 1.22-8.47 0.016 0.012
Pfizer w simul n/a No 0 1 1.1 0.00 0.00-16.74 0.468 0.468
Pfizer wo simul n/a No 2 1 0.7 2.67 0.20-78.89 0.472 0.394
1-42 43-84 GSK w simul n/a No 4 7 4.3 0.93 0.22-3.42 0.931 0.662
GSK wo simul n/a No 25 14 15.6 1.60 0.80-3.28 0.186 0.121
Pfizer w simul n/a No 1 3 3.5 0.29 0.01-4.25 0.428 0.957
Pfizer wo simul n/a No 3 3 3.4 0.88 0.14-5.47 0.888 0.718VSD RCA of RSV Vaccine in Older Adults
Surveillance Initiated on 01AUG2023, Analyses Based on Data Through 16MAR2024 (run #1, week #1836)
Concurrent Comparator Sequential Analysis Signal Assessment for Immune Thrombocytopenia
---Age:60+ yrs---
17
Analysis Parameters Signal Information and Informative Counts Nominal AnalysisSequential
Test
Outcome
EventRisk
Interval
DaysComp
Interval
DaysVaccine
TypeSignaled
in a
Prior
Run1New
Sequential
Analysis
Signal2Events
in Risk
IntervalEvents in
Comp
IntervalAdjusted
Expected
Events in
Risk
IntervalAdjusted
Rate
Ratio395%
Confidence
Interval42-sided
P Value1-sided
P Value5
ITP 1-21 43-63 GSK w simul n/a No 2 1 0.6 3.08 0.23-92.44 0.408 0.347
GSK wo simul n/a No 19 8 8.1 2.35 0.99-5.97 0.054 0.040
Pfizer w simul n/a No 0 1 0.2 0.00 0.00-81.18 0.810 0.810
Pfizer wo simul n/a No 2 2 1.8 1.10 0.11-11.27 0.931 0.659
22-42 GSK w simul n/a No 3 2 1.4 2.21 0.31-19.61 0.432 0.340
GSK wo simul n/a Yes 19 6 6.3 3.04 1.22-8.47 0.016 0.012
Pfizer w simul n/a No 0 1 1.1 0.00 0.00-16.74 0.468 0.468
Pfizer wo simul n/a No 2 1 0.7 2.67 0.20-78.89 0.472 0.394
1-42 43-84 GSK w simul n/a No 4 7 4.3 0.93 0.22-3.42 0.931 0.662
GSK wo simul n/a No 25 14 15.6 1.60 0.80-3.28 0.186 0.121
Pfizer w simul n/a No 1 3 3.5 0.29 0.01-4.25 0.428 0.957
Pfizer wo simul n/a No 3 3 3.4 0.88 0.14-5.47 0.888 0.718VSD RCA of RSV Vaccine in Older Adults
Surveillance Initiated on 01AUG2023, Analyses Based on Data Through 16MAR2024 (run #1, week #1836)
Concurrent Comparator Sequential Analysis Signal Assessment for Immune Thrombocytopenia
---Age:60+ yrs---
18
•ITP signal for GSK vaccine without simultaneous vaccination in
1-21 day risk interval versus 22 -42 day comparison interval
•Quick medical record reviews
-Of the 19 cases in the risk interval, 4 were incident ITP*
-Of the 14 cases in comparison intervals, 2 were incident ITP , 1 in the
22-42 day interval and 1 in the 43 -63 day interval
•After quick review: 4 cases of ITP in the primary risk interval, 1
case each in the 22 -42 and 43 -63 day comparison intervals
•Plan to do more detailed chart review of ITP cases going forwardITP Statistical Signal and Rapid Review
19*New cases of ITP relative to RSV vaccination.
GBS Cases Following RSV Vaccination
--No Statistical Signal --
20
GBS Cases 1 -84 Days after RSV Vaccination
•GBS cases identified electronically, then receive medical record review,
and presumptive cases are adjudicated by two reviewers
•Cases defined using Brighton Level (BL) criteria*
•7 cases of GBS (BL 1 -3) following any RSV vaccination
̶5 following GSK –  onset days 6, 10, 31, 54, 76
̶2 following Pfizer – onset days 9, 46
•2 BL 4 cases following GSKAutomated
CasesCompleted
Chart ReviewChart Confirmed
CasesNot
GBSCases Pending
Review
12 11 9 2 1
21*Sejvar  J, et al. Vaccine. 2011;29(3):599 -612.
22Analysis Parameters Signal Information and Informative Counts Nominal AnalysesSequential
Test
Outcome
EventRisk
Interval
DaysComp
Interval
Days Vaccine TypeSignaled
in a Prior
Run2New
Sequential
Analysis
Signal3Events
in Risk
IntervalEvents in
Comparison
IntervalAdjusted
Expected
Events in Risk
IntervalAdjusted
Rate
Ratio495%
Confidence
Interval52-sided
P value1-sided
P value6
GBS11-21 43-63 GSK wo simul No No 2 1 0.9 2.33 0.10-93.95 0.603 0.515
Pfizer wo simul No No 1 0 0.0 ne 0.05-ne 0.496 0.496
22-42 GSK wo simul No No 2 1 1.3 1.55 0.11-47.77 0.775 0.600
Pfizer wo simul No No 1 0 0.0 ne 0.07-ne 0.439 0.439
1-42 43-84 GSK wo simul No No 3 1 1.4 2.17 0.16-74.98 0.605 0.501
Pfizer wo simul No No 1 0 0.0 ne 0.04-ne 0.557 0.557---Age:60+ yrs---VSD RCA of RSV Vaccine in Older Adults
Surveillance Initiated on 01AUG2023, Analyses Based on Data Through 25MAY2024 (run #6, week #1846)
Concurrent Comparator Sequential Analysis Signal Assessment for Guillain -Barre Syndrome
(1) Chart -confirmed cases only, Brighton level 1 -3
(2) n/a = not applicable
(3) No prior signal, at least 2 events in the risk interval, 1 -sided P value < 0.014
(4) Adjusted for calendar date, VSD site, age category, sex, and race/ethnicity
(5) ne = not estimable
(6) Red: new sequential analysis signal, Yellow: 1 -sided P value < 0.014 but already signaled in a prior run
Crude GBS Incidence Rates after RSV Vaccination1
23Vaccine Risk interval# of
Cases# of
Doses2Rate Per Million
(95% CI)Rate per 100,000 PY
(95% CI)
GSK 1-21 days 2 323929 6.2 (0.7 – 22.3) 10.7 (1.3 – 38.8)
GSK 1-42 days 3 323929 9.3 (1.9 – 27.1) 8.1 (1.7 – 23.5)
Pfizer 1-21 days 1 45162 22.1 (0.6 – 123.4) 38.5 (1.0 – 214.6)
Pfizer 1-42 days 1 45162 22.1 (0.6 – 123.4) 19.3 (0.5 – 107.3)
VaccineComparison
interval# of
Cases# of
Doses3Rate Per Million
(95% CI)Rate per 100,000 PY
(95% CI)
GSK 43-84 days 2 301547 6.6 (0.8 – 24.0) 5.8 (0.7 -20.9)
Pfizer 43-84 days 1 41031 24.4 (0.6 – 135.8) 21.2 (0.5 – 118.1)
1Cases restricted to chart confirmed, Brighton Level 1 -3
2Vaccines administered 8 -1-23 through 4 -13-24
3Vaccines administered 8 -1-23 through 3 -2-24Risk interval estimates
Comparison interval estimates
•Background rate for GBS in persons 60+ years old: 1.4 -3.7 per 100,000 PY  (Sejvar , J., et al. Neuroepidemiol , 2011)
Atrial Fibrillation Following RSV Vaccination
--No Statistical Signal --
24
25Analysis Parameters Signal Information and Informative Counts Nominal AnalysisSequential
Test
Outcome
EventRisk
Interval
DaysComp
Interval
Days Vaccine TypeSignaled
in a
Prior
Run1New
Sequential
Analysis
Signal2Events
in Risk
IntervalEvents in
Comp
IntervalAdjusted
Expected
Events in
Risk
IntervalAdjusted
Rate
Ratio395%
Confidence
Interval42-sided
P value1-sided P
value5
AFIB 1-21 43-63 GSK w simul No No 81 75 76.7 1.06 0.75-1.49 0.756 0.411
GSK wo simul No No 198 232 222.3 0.89 0.72-1.10 0.282 0.871
Pfizer w simul No No 7 15 11.9 0.59 0.21-1.51 0.282 0.910
Pfizer wo simul No No 23 33 38.7 0.59 0.32-1.09 0.093 0.968
22-42 GSK w simul No No 91 109 106.9 0.85 0.63-1.14 0.282 0.876
GSK wo simul No No 211 222 209.8 1.01 0.83-1.22 0.954 0.497
Pfizer w simul No No 8 17 13.8 0.58 0.22-1.41 0.238 0.924
Pfizer wo simul No No 25 30 29.9 0.84 0.48-1.46 0.530 0.781
1-42 43-84 GSK w simul No No 190 155 166.7 1.14 0.90-1.44 0.267 0.146
GSK wo simul No No 422 441 444.2 0.95 0.82-1.10 0.496 0.764
Pfizer w simul No No 23 27 23.3 0.99 0.54-1.79 0.966 0.577
Pfizer wo simul No No 52 60 71.3 0.73 0.48-1.10 0.137 0.945VSD RCA of RSV Vaccine in Older Adults
Surveillance Initiated on 01AUG2023, Analyses Based on Data Through 25MAY2024 (run #6, week #1846)
Concurrent Comparator Sequential Analysis Signal Assessment for Atrial Fibrillation
---Age:60+ yrs---

•VSD initiated surveillance in older adults in January 2024
•385,729 doses of RSV vaccines have been administered to older adults
(88% GSK)
•Statistical signal for ITP in persons 60+ years old who received the GSK
RSV vaccine without simultaneous vaccination
-Most were not incident ITP cases with onset after RSV vaccination
-Plan for more detailed chart review of ITP in the fall
•No GBS signal, but few observed cases
•No other statistical signals observed to date
•Surveillance will continue for all outcomes, including GBS, through May
2025VSD RSV RCA Summary and Next Steps
26
RCA Study Team and Acknowledgments
27•Marshfield Clinic Research Institute: Ed Belongia, Hannah Berger, Kayla
Hanson, Burney Kieke, Dave McClure, Erica Scotty, Maria Sundaram, Jim
Donahue
•Centers for Disease Control and Prevention: Eric Weintraub, Tat’Yana
Kenigsberg, Amelia Jazwa , Tanya Myers, Mike McNeil, and Lily Wang
•Thank you to our colleagues at the other VSD sites: Kaiser Permanente
(Northern CA, Southern CA, Washington, Northwest, Colorado, Mid -
Atlantic), Denver Health, HealthPartners, and Harvard Pilgrim
•Many thanks to our colleagues at Kaiser Permanente Northern California
for their assistance with this project and their innovative analytic methods:
Bruce Fireman, Joan Bartlett, Kristin Goddard, Ned Lewis, and Nicky Klein
28The findings and conclusions in this presentation are those
of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention

Summary: Update: Rapid Cycle Analysis of RSV  Vaccines in Older Adults Jim Donahue, PhD DVM Marshfield Clinic Research Institute Presented to the ACIP June 26, 2024 1 RSV RCA Interim Report – June 26, 2024 •Description of Vaccine Safety Datalink and RCA •Review of surveillance methods •Descriptive analysis •Sequential analysis ̶Immune thrombocytopenia (ITP) ̶Guillain -Barré syndrome (GBS) ̶Atrial fibrillation 2 Vaccine Safety Datalink 2024 * 3•Collaborative project between CDC and 13 integrated…


06 RSV Adult Lloyd 508

1
Evaluation of Guillain -Barré Syndrome (GBS)
following Respiratory Syncytial Virus (RSV)
Vaccination Among Adults 65 Years and Older
Dr. Patricia Lloyd, ScM PhD
Health Statistician
Office of Biostatistics and Pharmacovigilance
Center for Biologics Evaluation and Research
U. S. Food & Drug Administration
MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)
Respiratory Syncytial Virus (RSV) Vaccine, Adults
June 26 – 28, 2024
2
Outline
•Introduction
•Observed vs. Expected Analysis Summary
▪Study Methods and Results
•Self-Controlled Case Series (SCCS) Analysis
▪Study Methods and Results
•Discussion
•Conclusion
3
Introduction
•Two* RSV vaccines were approved for use in the U.S. in adults 60 years and
older
▪RSVPreF3+AS01 (GSK - AREXVY)
▪RSVPreF (PFIZER - ABRYSVO)
•An imbalance in the rates of Guillain -Barré syndrome (GBS) between vaccine
and placebo recipients was identified in clinical trials supporting licensure of
RSV vaccines 1, 2
•FDA is conducting a post -licensure RSV vaccine safety study using two designs:
▪Observed vs. Expected Analysis
▪Self-Controlled Case Series (SCCS) Analysis
*mRNA -1345 (Moderna - mRESVIA ®) was approved on May 31, 2024.
4
Observed vs. Expected Analysis Summary
Methods
•Evaluated risk of GBS following one dose of either RSVPreF3+AS01
or RSVPreF vaccines using a retrospective cohort design with the
2022 historical comparator
•Estimated the observed incidence rates (IRs) and compared to
historical comparator (expected) rates, to obtain incidence rate
ratios (IRRs) with 95% confidence intervals (CIs)
•Estimation of GBS positive -predictive value (PPV) -adjusted rates is
based on multiple imputed datasets
▪Chart review, PPV for GBS: 71% (95% CI: 63%, 79%) 3
5
Observed vs. Expected Analysis Summary
Results
RSVPreF3+AS01 RSVPreF
Inferential Analysis Results
Observed vs. Expected Analysis 2.76 (95% CI: 1.32, 5.07) 6.94 (95% CI: 3.70, 11.87)
PPV-Adjusted Analysis 2.75 (95% CI: 0.46, 5.04) 6.91 (95% CI: 1.85, 11.97)
GBS Cases per 1 million Doses 10.0 25.1
Descriptive Analysis Results
Total RSV Vaccine Doses 2,061,602
RSV Vaccine Doses 1,379,335 682,267
Observed GBS cases <11 13
Data Through Date: Dec 02, 2023•An elevated IRR was observed for GBS following RSV vaccination
•Only RSVPreF association was statistically significantly elevated in PPV -adjusted analysis
6
•The observed vs. expected analysis is a crude method with
limited adjustments for confounding, utilizing aggregate
historical incidence rates rather than individual historical persons
as comparators, increasing the potential for confounding and
bias
•The SCCS is a robust method that controls for time -invariant
confounding and does not rely on historical background
incidence ratesMotivation for SCCS Study
7
Self-Controlled Case Series (SCCS) Design
•Population Exclusion Criteria:
▪Beneficiaries with no incident
GBS outcome in the
observation period
OR
▪Beneficiaries who do not
meet criteria to identify an
incident outcome**
Days  43-90 Days 1 -42
365 Days Prior
Study Start Date
May 2023Study End Date
Apr 2024
RSV Vaccination (Day 0)= Risk Interval
= Control Interval
= GBS Outcome
*The clean window is relative to the outcome date; risk and control intervals are relative to the vaccination date
**Outcomes that are considered ‘incident’ after implementing the outcome -specific cleaning window are included,
and only first incident outcome in the observation period are retained•Population Inclusion Criteria:
▪Enrolled in Medicare Fee -
for-Service (FFS) during the
clean window
▪65 years of age or older on
RSV vaccination date
▪No GBS outcome during the
clean window= Clean Window (365 days)*
8
SCCS Analysis: Study Methods
Study Design Self-Controlled Case Series (SCCS) 4, 5
Data Sources and
Study PopulationCenters for Medicare & Medicaid Services (CMS)  Medicare Beneficiaries ages 65 years
and older, enrolled in:
▪Medicare FFS (Parts A and B) and Part D on the date of RSV vaccination
▪Medicare FFS and in 1 -year prior
Study Period May 2023* – April 2024 ⬧**
GBS Outcome
Definition▪Risk Interval: 1 - 42 days
▪Control Interval: 43 - 90 days
▪Care Setting: inpatient – primary position only; ICD -10-CM DGN G61.0
Statistical
Analyses▪IRRs with 95% CIs
▪Absolute Risk: Attributable Risk (AR) with 95% CIs per 100,000 doses and 100,000
person -years (PY)
▪Adjustment for outcome -dependent observation time (Farrington) 6, seasonality, PPV
*FDA approval dates for RSVPreF3+AS01 and RSVPreF were May 3, 2023 and May 31, 2023, respectively
⬧Study end date for initial SCCS analysis was April 6, 2024
**RSV vaccinations prior to October 8, 2023 to have complete observation in 90 days post -vaccination and is expected to have 90%  or greater data -completeness
9
SCCS Analysis: Vaccination Uptake Trends
020,00040,00060,00080,000100,000120,000140,000160,000180,000200,000Number of RSV Vaccinations
Calendar WeekWeekly Vaccination Uptake Trends in RSV Vaccines, By Vaccine Type
RSVPreF RSVPreF3+AS01
 Vaccination Cut -off Date to ensure complete observation of 90 -day window
Data Through Date: Apr 06, 2024
10
Case Population Eligibility
CriteriaRSV Vaccinations
(n=1.33 M individuals; 1.33 M doses)*
RSVPreF3+AS01
(n= ~872k doses)*RSVPreF
(n= ~456k doses)*
Total GBS cases and total number
of days in study period160 cases [339 days] 92 cases [311 days]
GBS cases  during 90 -day
observation period 105 74
Incident GBS cases after applying
clean window restriction55 36
GBS cases qualifying for SCCS
analysis
(vaccinated before Oct 8, 2023)11 17Case Counts for GBS following RSV vaccination by Vaccine Type
* n = Medicare Beneficiaries that received RSV vaccination and eligible for SCCS analysis are presentedSCCS Analysis: Descriptive Results
Data Through Date: Apr 06, 2024
11
 Data Through Date: Apr 06, 2024SCCS Analysis: Results for GBS
Most Adjusted
Analysis
Least
Adjusted
Analysis
SCCS Analysis including most adjustments are highlighted in Blue
Farrington -Adjusted Analysis = Outcome -Dependent Observation Time AdjustmentIRR with 95% CI of GBS following RSV Vaccination Adjusted for Combinations of PPV,
Seasonality with Outcome -Dependent Observation Time
•An elevated IRR was observed for GBS following RSVPreF vaccination with two analyses that had the least adjustments
•Results additionally adjusted for PPV were no longer statistically significant
▪PPV, Seasonality with Farrington -Adjusted Analysis: 4.48 (95% CI: 0.88, 22.90) ▪PPV, with Farrington -Adjusted Analysis: 3.96 (95% CI: 0.77, 20.28)
Seasonality,
Farrington
FarringtonPPV, FarringtonPPV, Seasonality,
FarringtonAnalyses
12
SCCS Analysis: Results for GBS and
RSV vaccination
Inferential Analysis Results RSVPreF3+AS01 RSVPreF
Eligible Vaccinees 872,068 456,107
Cases in the Risk and Control
Intervals<11 12.1
IRR (95% CI) 2.30 (0.39, 13.72) 4.48 (0.88, 22.90)
AR per 100,000 Doses (95% CI) 0.32 ( -0.30, 0.95) 1.57 (0.30, 2.85)
AR Per 100,000 PY (95% CI) 2.81 ( -2.64, 8.26) 13.69 (2.59, 24.79)Incidence Rate Ratio (IRR) and Attributable Risk (AR) of GBS - Adjusted for PPV, Seasonality and
Outcome -Dependent Observation Time
Data Through Date: Apr 06, 2024
13
•SCCS study design provides
robust adjustment for potential
time-invariant confounding
•Large database facilitates
more precise evaluation of
health outcomes
•Study findings are
generalizable to U.S.
population 65 years and olderDiscussion
Strengths Limitations
•Potential outcome
misclassification
•Potential misspecification of
risk and control intervals
•Potential for residual
confounding
14
Discussion
Observed vs. Expected Analysis
•An elevated IRR was observed for GBS following RSV vaccination,
but only RSVPreF association was statistically significantly elevated
PPV (chart review) adjustment
•Crude method that utilized aggregate historical comparator rates
rather than individuals, increasing the potential for confounding
•Statistically significant results of GBS do not establish a causal
association between RSV vaccines and GBS
15
Discussion
SCCS Analysis
•Although, an elevated IRR was observed for GBS following
RSVPreF vaccination for two analyses that had fewer adjustments,
the results were not statistically significant when adjusted for PPV
•Only cases, i.e., persons with an incident outcome contribute to the
SCCS analysis
•Estimation of outcome risk occurs within, rather than between
individuals, adjusting for time -invariant confounding
16
Conclusion
•The results from two different types of analyses of potential GBS risk
following RSV vaccination are mixed and highly uncertain
•These analyses do not provide clear, conclusive evidence of an elevated
risk of GBS and an elevated risk cannot be ruled out at this time
•FDA is conducting medical chart review on GBS cases and will continue to
evaluate the safety of RSV vaccines as more data are available
•FDA maintains that the b enefits of RSV vaccination in preventing RSV
hospitalizations outweigh the potential risks associated with the vaccines
References
17
1.Respiratory Syncytial Virus Vaccine Recombinant, Adjuvanted ( Arexvy ). Vaccines and Related Biological
Products Advisory Committee Meeting. FDA Briefing Document. March 1, 2023.
https://www.fda.gov/media/165622/download
2.Respiratory Syncytial Virus Stabilized Bivalent Prefusion F Subunit Vaccine ( Abrysvo ). Vaccines and
Related Biological Products Advisory Committee Meeting. FDA Briefing Document. March 1, 2023.
https://www.fda.gov/media/165625/download
3.Arya,D.P ., et al. Surveillance for Guillain -Barré syndrome after 2015 -2016 and 2016 -2017 influenza
vaccination of Medicare beneficiaries. Vaccine, 2019. 37(43): p. 6543 -6549.
4.Petersen I, Douglas I, Whitaker H. Self controlled case series methods: an alternative to standard
epidemiological study designs. 2016;354:i4515.
5.Evaluation of Multiple Safety Outcomes following RSV Vaccination in Adults 60 Years and Older.
https://bestinitiative.org/wp -content/uploads/2024/01/BEST_RSV_Safety_Older_Adults_2023 -2024.pdf
6.Farrington, C. P., Anaya -Izquierdo , K., Whitaker, H. J., Hocine , M. N., Douglas, I., & Smeeth, L. (2011). Self -
Controlled Case Series Analysis With Event -Dependent Observation Periods. Journal of the American
Statistical Association, 106(494), 417 –426. https://doi.org/10.1198/jasa.2011.ap10108
Acknowledgements
18
Steven Anderson
Richard Forshee
Narayan Nair
Joann Gruber
Carla Zelaya
Tainya Clarke
FDA Partners:
Acumen, CMS
Questions?
19

Summary: 1 Evaluation of Guillain -Barré Syndrome (GBS)  following Respiratory Syncytial Virus (RSV)  Vaccination Among Adults 65 Years and Older Dr. Patricia Lloyd, ScM PhD Health Statistician Office of Biostatistics and Pharmacovigilance Center for Biologics Evaluation and Research U. S. Food & Drug Administration MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) Respiratory Syncytial Virus (RSV) Vaccine, Adults  June 26 – 28, 2024 2 Outline •Introduction •Observed vs. Expected…