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© 2025 Moderna, inc. All rights reserved.RSV Vaccine (mRNA -1345) Update:
-Safety & Immunogenicity in 18-59 Year Olds
at increased Risk for RSV Disease *
-Revaccination of Adults at 12 or 24 Months *
ACIP
Frances Priddy, MD MPH
April 16, 2025
* mRESVIA has not been authorized for these indications
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RSV Vaccine (mRNA -1345) Clinical Development
NCT05127434, NCT05330975, NCT06060457, NCT06067230
Efficacy, Immunogenicity, Safety, and Correlate of Protection
Adults ≥60 years
Study 301
Adults ≥50 years
Study 302 - Part A and B
Concomitant Administration
with Standard Dose Influenza or
COVID -19
Adults ≥65 years
Study 304
Concomitant Administration
with High Dose Influenza
Adults 18-59 years
Study 303 – Part A
Safety and Immunogenicity in
Adults at Increased Risk
Adults ≥50 years
Study 302 – Part CAdults ≥60 years
Study 301 – Part BAdults with SOT ≥18 years
Study 303 – Part B
12 Month Revaccination
24 Month Revaccination
Safety and Immunogenicity in
Immunocompromised
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Adult RSV hospitalizations
•37% in 18-64-year -olds
•24% in 50-64-year -olds
•22% required ICU
admission
•3% in-hospital mortalityComorbidityIncidence rate ratio for those with versus those
without comorbidity among adults 18-64 years
0 40
Asthma2.0 – 3.6
CAD0.9 – 7.0
Diabetes3.4 – 11.4
COPD3.2 – 6.4
CHF*13.3 – 33.2US Hospitalization Rates for RSV in 18-64 Year Olds with
Underlying Conditions
CAD - coronary artery disease; CHF - congestive heart failure; COPD - chronic obstructive pulmonary disease; RSV - respiratory syncytial virus
*CHF age 20-59 years
Branche AR, et al. Clin Infect Dis. 2022.
RSV-NET Analysis –Adults Hospitalized
with Laboratory Confirmed RSV
2016 -2023 (N=16,575)Estimated incidence of RSV-associated Hospitalization
in 2 Regions of New York State, US, 2017 -2020 (N=1099)
Havers FP, et al. JAMA Netw Open . 2024.
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© 2025 Moderna, inc. All rights reserved.mRNA -1345 in Adults,18 -59 Years,
at Increased Risk of RSV Disease
Study 303, Part A
ISIRV 2025
5Study Design – Randomized Double -Blind Study in
18-59-Year -Old Adults at Increased Risk of RSV Disease
Study 303, Part A
Coronary Artery Disease (CAD)
and/or
Congestive Heart Failure (CHF)mRNA -1345 Dose
COPD, Persistent Asthma , Pulmonary
Fibrosis, and/or Other Chronic
Respiratory DiseasesUnderlying Disease Category
50 µg
N ~ 150
50 µg
N ~ 150
50 µg
N ~ 200Diabetes Mellitus 1 or 2•Day 29 immunogenicity
compared between this
population and adults
≥60 years in pivotal
efficacy trial
•Participants followed for
24 months
United States
Canada
United Kingdom
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Comparison of seroresponse rates (SRR) of 50 µg high-risk 18-59 years olds vs
50 µg ≥ 60-year -olds in pivotal efficacy study
•Criteria for Noninferiority: 95% CI of SRR difference LB > -10%
Secondary ObjectiveKey Study Objectives
Study 303, Part A
Primary Objectives
1.Safety and tolerability of the vaccine in high-risk 18-59-year -olds
2.Compare RSV-A and RSV-B GMTs at Day 29 after a single dose of 50 µg in
high-risk adults, 18-59 years, versus adults ≥60 years in the pivotal phase 2/3
efficacy trial
•Criteria for Noninferiority: 95% CI of GMR LB > 0.667
© 2025 Moderna, inc. All rights reserved.LB – lower bound, CI – confidence interval; GMR – geometric mean ratio; SCR – seroconversion rate; SRR – seroresponse rate
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(stage 0,1,2,3,4)
© 2025 Moderna, inc. All rights reserved.Underlying Medical Conditions of Study Participants
Physician -documentation required for all underlying medical conditions
•CAD
•CHF*
•Chronic respiratory disease
− COPD*
− Persistent asthma – requiring ≥1 maintenance medication
− Pulmonary fibrosis
− Other chronic lung disease
•Stable type 1 or type 2 diabetes mellitus
− Controlled with ≥1 medication started 90 days prior to Day 1
CAD, coronary artery disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; RSV, respiratory syncytial virus.
*Severity of CHF and COPD assessed at baseline using NYHA Functional Classification for CHF (stage I, II, III, IV), or modified MRC Dyspnea Scale for COPD
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Sept 18, 2024 data cutoff
© 2025 Moderna, inc. All rights reserved.Demographics of Study Participants
Study 303, Part A, Safety Set
mRNA -1345 (50 µg)
Medical History Category18-59 years
N = 50250-59 years
N = 306
Median Age, years (range) 53 (19-59) 56 (50-59)
Female, n (%) 269 (54%) 158 (52%)
Race/Ethnicity, n (%)
White 401 (80%) 238 (78%)
Black or African American 85 (17%) 64 (21%)
Asian 4 (1%) 2 (1%)
Hispanic / Latino Ethnicity 140 (28%) 88 (29%)
•Study population was racially/ethnically diverse
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Safety – mRNA -1345 in Adults,
18-59 Years, at Increased Risk of
RSV Disease
Study 303, Part A
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Local Reactions - Vaccine Generally Well Tolerated in Adults,
18-59 Years, at Increased Risk for RSV Disease
Solicited Local Reactions within 7 Days of Injection compared to Older Adults ≥60 Years
Solicited Safety Set – Studies 303 Part A (N = 502) & 301 (N = 18,160)
74%
56%
2% 2%5% 4%17%15%
0%20%40%60%80%100% Injection Site Injection Site Injection Site Axillary Swelling
Pain Erythema Swelling or Tenderness
Grade 3 or 4
Grade 2
Grade 1
Study 303
Sept 18, 2024 data cutoff - Study 303
© 2025 Moderna, inc. All rights reserved.Study 301 Study 303 Study 301 Study 303 Study 301 Study 303 Study 301
•Injection site pain was more common among high -risk adults, 18-59 years, than adults ≥ 60 years
•Rates of other local reactions generally similar across age groups
•Mostly grade 1 -2, onset days 1-2; median duration of 2 days; 1 grade 4 pain
11Systemic Reactions - Vaccine Generally Well Tolerated in
Adults, 18-59 Years, at Increased Risk for RSV Disease
Solicited Systemic Reactions within 7 Days of Injection compared to Older Adults ≥60 Years
Solicited Safety Set – Studies 303 Part A (N = 502) & 301 (N = 18,160)
4% 3%33%
27%37%
31%29%26%23% 22%
11%7%20%
12%20%40%60%80%100%Nausea/
VomitingChills
0%
Study 303 Study 301 Study 303 Study 301 Study 303 Study 301 Study 303 Study 301 Study 303 Study 301 Study 303 Study 301 Study 303 Study 301
•Rates of systemic reactions generally similar or slightly higher among 18-59-year -olds vs adults ≥60 years old
•Mostly grade 1-2, onset days 1-2; median duration of 2 days; no grade 4 reactions
Fever Headache Fatigue Myalgia Arthralgia
Grade 3
Grade 2
Grade 1
Sept 18, 2024 data cutoff – Study 303
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•No anaphylaxis, thrombocytopenia, Guillain -Barré syndrome, acute disseminated
encephalomyelitis (ADEM), or acute myocarditis or acute pericarditisUnsolicited Adverse Events Within 28 Days After mRNA -1345
Regardless of Relationship to Study Vaccination
Study 303, Part A - Adults at Increased Risk of RSV – Safety Set
Sept 18, 2024 data cutoff
30 µg, N=497; 50 µg, N=502
* 30 µg group, 50-59 year olds, unrelated to study injection by investigator: one case of pneumonia, one case of asthma exacerbation, both RSV RT-PCR negative
© 2025 Moderna, inc. All rights reserved.mRNA -1345
18-59 years
Total = 999mRNA -1345
50-59 years
N = 607
All, n (%) 226 (22.6%) 131 (21.6%)
Non-Serious 224 (22.4%) 129 (21.3%)
Serious 2 (0.2%)* 2 (0.3%)*
Fatal 0 0
Medically -Attended 117 (11.7%) 68 (11.2%)
Leading to Study Discontinuation 0 0
Severe 2 (0.2%)* 2 (0.3%)*
Any Adverse Event of Special Interest (AESI) 0 0
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Immunogenicity – mRNA -1345 in
Adults,18 -59 Years, at Increased Risk
of RSV Disease
Study 303, Part A
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mRNA -1345 Vaccination (50 µg) in Adults,18 -59 Years at
Increased Risk of RSV Disease Meets Pre-Specified Noninferiority
Criteria -RSV-A and RSV-B
Study 303, Part A & Study 301
GMR – Geometric mean ratio; Sept 18, 2024 data cutoff0.667
AntibodyGMR (95% CI)
at Month 1
RSV-A Neutralizing Antibody (IU/mL) 1.16 (1.05, 1.29)
RSV-B Neutralizing Antibody (IU/mL) 1.14 (1.04, 1.24)
0.5 1
GMR (95% CI)2 1.5
•All GMR non-inferiority criteria met (LB of the 2-sided 95% CI of GMR > 0.667)
comparing 18-59-year -olds vs ≥60-year -olds in efficacy trial
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15RSV-A Neutralizing Antibody GMT after 50 µg of mRNA -1345 in
Adults, 18-59 Years, at Increased Risk of RSV Disease, by Age
Study 303, Part A
100000
RSV-A GMT comparable between 18-49 and 50-59 year olds
1432164718977 19271
10010001000018-49 Years (N=189) 50-59 Years (N=305)
© 2025 Moderna, inc. All rights reserved.GMT
(95% CI)
RSV-AD1 D29 D1 D29
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RSV-B Neutralizing Antibody GMT after 50 µg of mRNA -1345 in
Adults, 18-59 Years, at Increased Risk of RSV Disease, by Age
RSV-B GMT comparable between 18-49 and 50-59 year olds
93910936678 6745
100100010000Study 303, Part A
18-49 Years (N=189) 50-59 Years (N=305)
© 2025 Moderna, inc. All rights reserved.GMT
(95% CI)
D1 D29 D1 D29
RSV-B
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RSV-A Neutralizing Antibody GMT after 50 µg of mRNA -1345 in Adults, 18-59
Years, at Increased Risk of RSV Disease by Primary Risk Factor and BMI
Study 303, Part A
GMT; Geometric Mean Titer
15611678
1527 15801511 1590 1578148219158 19036 19905
1678120675 1891520320
100100010000100000
GMT
(IU/mL)All High -Risk
Adults
18-59 YearsCoronary
Artery Disease/
Congestive
Heart Failure
20140BMI < 30
kg/m2Chronic Lung Diabetes
DiseaseBMI ≥ 30
kg/m2BMI < 40
kg/m2BMI ≥ 40
kg/m2
D1 D29 D1 D29 D1 D29 D1 D29 D1 D29 D1 D29 D1 D29 D1 D29
RSV-A
•Individuals with medical risk factors for RSV show consistent RSV-A neutralizing antibody responses
compared to entire study population; no impact of BMI on antibody response
•Similar results for RSV-B
GBS – Guillain -Barré syndrome, ADEM – acute disseminated encephalomyelitis
© 2025 Moderna, inc. All rights reserved.
18Summary – RSV Vaccine (mRNA -1345) in Adults,
18-59 Years, at Increased Risk of RSV Disease
•Vaccine generally well tolerated across all ages
•No safety concerns identified (no reports of thrombocytopenia, GBS, ADEM,
acute myocarditis and/or pericarditis)Safety
•RSV-A & RSV-B immune responses non-inferior to adults ≥60 years in pivotal
efficacy trial; similar efficacy inferred
•Immunogenicity consistent across age groups, including 50-59 years, and
underlying medical conditionsImmunogenicity
•Substantial burden of RSV-associated hospitalizations in adults, 18-59 years
•mRNA -1345 has the potential to also protect adults, 18-59 years, at increased
risk of severe RSV disease
•Data under review by FDA; PDUFA date June 12, 2025Public Health
Impact
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Revaccination of Healthy Adults
at 12 or 24 Months
ESCMID 2025
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20RSV Case Accrual and Efficacy Analyses through 3 Seasons
in the Phase 2/3 Pivotal Trial
Study 301
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9
8
7
6
5
4
3
2
1
0
2021 2022 2023 2024
1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -
impacted -hospitalizations.html 2. Based on final FDA Package InsertOverall US
2021 -2023 RSV
Hospitalization
Rate per
100,000 Adults
≥ 65 Years1
2021 -2022
RSV Season 12022 -2023
RSV Season 22023 -2024
RSV Season 3LRTD 2+
CasesPrimary Analysis
Nov ‘21 – Nov ’2285
174Efficacy2
50.3%
(37.5%, 60.7%)LRTD 2+
62.5%
(47.7%, 73.1%)78.7%
(62.8%, 87.9%)
Durability through
Season 2
Nov ‘21 – Apr ‘23
Durability through
Season 3
Nov ‘21 – Mar ‘2456.7%
33.1%, 72.6%)Severe RSV
(shortness of
breath)
74.6%
(50.7%, 86.9%)86.7%
(41.9%, 97.0%)
338
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Vaccination Regimens – Revaccination Studies in Adults
Study 302 & Study 301 (50 µg)
Day 1 12 Months
RSV Vaccine
(mRNA -1345)N
RSV Vaccine
(mRNA -1345)544
RSV Vaccine
(mRNA -1345)1502RSV Vaccine
(mRNA -1345)24 MonthsRevaccination
PlaceboStudy 302
≥50 Years
© 2025 Moderna, inc. All rights reserved.Study 301
Part B
≥60 Years2:1
Vaccine: Placebo
12-month data presented at June 2024 ACIP meeting
22Revaccination at 12 Months with mRNA -1345 Meets
Pre-Specified Noninferiority Criteria -RSV-A
Study 302C – Adults ≥50 Years – Per Protocol Set (N=524)
214818283
455419662
100100010000100000
1 2 3 4 5 9 10 11 12 13 14
Part C
12 Month Revaccination0
Part B
Dose 16 7 8
Study MonthRSV-A Neutralizing Antibody
GMT
(IU/mL)
•RSV-A neutralizing antibodies detectable at 12 months post-vaccination
•Revaccination 1 year after primary vaccination elicits responses similar to those following primary dose
•Revaccination met non-inferiority success criteria for RSV-A & RSV-B (LB of 95% CI of GMR > 0.667)
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© 2025 Moderna, inc. All rights reserved.24 Month Revaccination – Demographics of Study Participants
Study 301, Part B, Safety Set
mRNA -1345 (50 µg)
N = 998
Age (Years) Median (range) 68.0 (60-91)
Sex, n (%) Female 508 (51%)
White 798 (80%)
Race/Ethnicity, n (%)Black or African American 161 (16%)
Asian 14 (1%)
Hispanic / Latino Ethnicity 234 (23%)
≥1 Comorbidity 321 (32%)
Diabetes (Type 1 or 2) 194 (19%)
Asthma 85 (9%)
Comorbidities, n (%) Chronic Obstructive Pulmonary Disease (COPD) 54 (5%)
Advanced Liver or Renal Disease 11 (1%)
Chronic Heart Failure (CHF) 13 (1%)
Chronic Respiratory Disease 2 (0.2%)
Body Mass Index, n (%) ≥30 kg/m2 317 (32%)
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© 2025 Moderna, inc. All rights reserved.Safety –
Revaccination at 24 Months
SAE – serious adverse event; AESI – adverse event of special interest
End of study analysis (last subject last visit Oct 23, 2024)
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Safety - Revaccination at 24 Months with mRNA -1345
Study 301B, Adults ≥60 Years (N=998)
•Revaccination generally well tolerated
•Local and systemic reactions were mainly Grade 1-2, with median onset on
Day 2, and median 2-day duration
•Comparable to reactogenicity after primary dose
•No safety concerns identified
•No reports of:
•Deaths, SAEs, or AESIs as assessed as vaccine -related by the investigator
•Anaphylaxis
•Guillain Barre Syndrome
•Acute disseminated encephalomyelitis (ADEM)
•Acute myocarditis or acute pericarditis
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© 2025 Moderna, inc. All rights reserved.Immunogenicity –
Revaccination at 24 Months
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Revaccination at 24 Months with mRNA -1345 Meets
Pre-Specified Noninferiority Criteria -RSV-A
Study 301B – Adults ≥60 Years – Per Protocol Set (N=956)
204817157
417512340
1000
100
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Dose 1 Study Month 24 Month Revaccination10000100000
GMT
(IU/mL)RSV-A Neutralizing Antibody
•RSV-A neutralizing antibodies detectable at 24 months post-vaccination
•Revaccination at 24 months after primary vaccination elicits responses similar to those following primary dose
•Revaccination met non-inferiority success criteria for RSV-A & RSV-B (LB of 95% CI of GMR > 0.667)
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Predicted Vaccine Efficacy for the 12-Month Period Following
24 Month Revaccination with mRNA -1345
Neutralizing AntibodyDay 29
GMT After
Revaccination RSV-LRTD 2+ RSV-LRTD 3+
RSV-A (IU/mL) 1238260%
(43, 74)68%
(44, 84)
RSV-B (IU/mL) 402458%
(40, 73)67%
(44, 84)
0.0 0.2 0.4 0.6 0.8 1.0
Predicted Vaccine
Efficacy (95% CI)
0.0 0.2 0.4 0.6 0.8 1.0
Predicted Vaccine
Efficacy (95% CI)
© 2025 Moderna, inc. All rights reserved.Study P301 Part B Per-Protocol Set ≥60 Years, N = 956
Correlate of protection model suggests revaccination restores vaccine efficacy
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Summary – RSV Vaccine (mRNA -1345) Revaccination
•Revaccination generally well tolerated; no safety concerns identified
•No reports of GBS, ADEM, acute myocarditis and/or pericarditis
•Durability of immune response demonstrated out to 24 months
•Revaccination at 12 or 24 months:
•Restores immune response; met noninferiority criteria
•Expected to provide comparable vaccine efficacy to that after
primary doseSafety &
Immunogenicity
•Revaccination has the potential to provide sustained protection
against RSVPublic Health
Impact of
Revaccination
© 2025 Moderna, inc. All rights reserved.GBS – Guillain -Barré syndrome, ADEM – acute disseminated encephalomyelitis
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© 2025 Moderna, inc. All rights reserved.THANK YOU!•Investigators
•Study site personnel
•Laboratory personnel
•Most importantly, the individuals who
participated in these trials