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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