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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
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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
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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
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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.
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▪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
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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
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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
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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
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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
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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
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Efficacy Analyses
Study 301
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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
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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
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Persistence of RSV Antibody and Revaccination
at 12 Months
Study 302
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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
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SUMMARY
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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
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THANK YOU!
24▪Investigators
▪Study site personnel
▪Laboratory personnel
▪Most importantly, the individuals who
participated in these trials