Document text
© 2024 Moderna, inc. All rights reserved.RSV Vaccine ( mRESVIA , mRNA -1345)
Concomitant Administration Overview
Advisory Committee on Immunization Practices
Rituparna Das, MD PhD
Oct 24, 2024
1
© 2024 Moderna, inc. All rights reserved.
Cumulative Burden of Seasonal Respiratory Viruses in US Older Adults
RSV Influenza2
Cumulative US
Hospitalization Rate
(≥65 yr, rate/100,000, 9/28/2024)1 227 106
US Vaccine Coverage
2023 -242-4
(COVID -19 & Flu ≥65 yrs, RSV ≥60 yrs)70% 23%
1.CDC RESP -NET, MMWR week 39, week ending 9/28/2024, https://www.cdc.gov/resp -net/dashboard/index.html accessed 10/18/2024 ; 2. CDC COVIDVaxView
https://www.cdc.gov/covidvaxview/ ; 3. CDC FluVaxView https://www.cdc.gov/covidvaxview/ ; 4. CDC RSVVaxView https://www.cdc.gov/rsvvaxview/ 5. Bonanni et al
Human Vaccines Immuno 2023; 6. NVAC Pediatrics. 2003;. 7. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/timing.html#ref -13; 8. Britton et al. MMWR 2024
https://www.cdc.gov/mmwr/volumes/73/wr/mm7332e1.htmCOVID -19
811
39%
Concomitant administration of vaccines is an effective method to increase vaccine coverage.
MMWR: Coadministration of RSV vaccines with other adult vaccines during the same visit is
acceptable5-8
© 2024 Moderna, inc. All rights reserved.
mRNA 1345 Clinical Development
NCT05127434, NCT05330975, NCT060604573
Adults ≥60 years
Study 301
Efficacy, Immunogenicity, Safety, and Correlate of Protection
Concomitant Administration
with Standard Dose Influenza
Adults ≥50 years
Study 302 - Part B
Concomitant Administration
with COVID -19
Adults ≥65 years
Study 304
Concomitant Administration
with High Dose Influenza
Adults ≥50 years
Study 302 - Part A
© 2024 Moderna, inc. All rights reserved.
Summary of Today’s Presentation4
1. ACIP, Feb 2024 Study 302 Parts A & B – Supports coadministration of mRNA -1345 with standard dose influenza and
COVID -19 vaccines (previously presented)1
•Well tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains, COVID -19, and RSV
Study 304 – Data for coadministration of mRNA -1345 with high -dose influenza vaccine
•Well-tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains and RSV
•RSV titers lower with coadministration; data from correlate of protection model demonstrate
that clinical efficacy against RSV disease, including severe disease, is likely maintained
Overall, the benefit: risk of coadministration of mRNA -1345 with standard and high -dose influenza
vaccines, and COVID -19 vaccine is positive
© 2024 Moderna, inc. All rights reserved.
RSV Case Accrual and Efficacy Analyses through 3 Seasons
in the Phase 2/3 Pivotal Trial
Study 3015
012345678910
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 1Durability through
Season 2
Nov ‘21 – Apr ‘23Primary Analysis
Nov ‘21 – Nov ’22
2022 -2023
RSV Season 2Durability through
Season 3
Nov ‘21 – Mar ‘24
2023 -2024
RSV Season 3
2021 2022 2023 2024LRTD 2+
Cases
85 78.7%
174Efficacy2
50.3%
(37.5%, 60.7%)56.7%
33.1%, 72.6%)LRTD 2+Severe RSV
(shortness of
breath)
62.5%
(47.7%, 73.1%)74.6%
(50.7%, 86.9%)78.7%
(62.8%, 87.9%)86.7%
(41.9%, 97.0%)
338
© 2024 Moderna, inc. All rights reserved.
Predicted Efficacy
•Coadministration efficacy
•Revaccination efficacy
INPUT from Phase 3 Pivotal Efficacy Trial
(Study 301)RSV Correlate of Protection Model
Preplanned case -cohort design6
1597
mRNA -1345
Recipients
533
Placebo
Recipients
271
RSV ARD
Cases1
OUTPUT
•Day 1 and Day 29 sera collected from all study participants
•Evaluated for RSV -A and B neutralizing titers, and Pre -F binding titers
•Objective to determine the relationship between immunogenicity and efficacy to identify
correlates of protection
1.Includes 174 LRTD2+ and 70 LRTD3+ RSV cases; Ma, C et al, RSVVW, 2024
© 2024 Moderna, inc. All rights reserved.
Correlate of Risk Antibodies are a Correlate of Risk and Correlate of
Protection for RSV
Study 301 – LRTD2+ RSV Efficacy7
The panels demonstrate the Correlate of Risk (A) and Correlate of Protection (B) analysis for the RSV -LRTD 2+ endpoint by Day 29 RSV -A neutralizing antibody.
A.The red and blue solid curves demonstrate the point estimate of the predictive risk for vaccine and placebo recipients at eac h assigned antibody titer. The red and blue dashed curves along with the
shaded area represent the bootstrap point -wise 95% confidence interval (CI).
B.The solid black curve shows the point estimate of controlled vaccine efficacy at each assigned antibody titer and the dashed curves demonstrate the bootstrap point -wise 95% CI.
102 103 104 105
Day 29 RSV -A Neutralizing Antibody Titer
(IU/mL)Probability
of RSV0.035
0.030
0.025
0.020
0.010
0.0050.015RSV-A Neutralizing Antibody
mRNA -1345 50 g
PlaceboCorrelate of Protection
102 103104 105
Day 29 RSV -A Neutralizing Antibody Titer
(IU/mL)Estimated
Vaccine
Efficacy1.0
0.8
0.6
0.2
00.4
© 2024 Moderna, inc. All rights reserved.
Concomitant Administration
of mRNA -1345 with High -Dose
Influenza Vaccine
Study 3048
© 2024 Moderna, inc. All rights reserved.
Study Design – Concomitant Administration of
mRNA -1345 & Fluzone HD
Study 304 - Phase 3, Randomized, Observer -Blind Trial
United States
Day 22Day 1
Stratified by age: 65–74 and ≥75 years (20%)
Study duration: ~8 months per participantFluzone HD +
mRNA -1345 Fluzone HD +
Placebo
Placebo mRNA -1345Vaccine
RegimenGroup 2
(Sequential administration)1:1 Randomization
~1900 adults ≥65 years of age
Group 1
(Concomitant administration)9
© 2024 Moderna, inc. All rights reserved.
110100100010000100000
Baseline Day 22 Baseline Day 22Concomitant Administration Results in Robust RSV and
Influenza Responses Across All Adults ≥65 Years
Study 304
GMT; Geometric Mean TiterGroup 1
D1: Flu HD + mRNA -1345
D22: PlaceboGroup 2
D1: Flu HD + Placebo
D22: mRNA -1345
Group 1 Group 2GMT
(95% CI)10
RSV-A Neutralizing Antibody Influenza A/H3N2, HAI
1101001000
Baseline Day 22 Baseline Day 22
Group 1 Group 2
© 2024 Moderna, inc. All rights reserved.
Co-Primary Immunogenicity Endpoint Evaluation
GMR (95% CI)
Influenza A/H1N1 0.87 (0.78, 0.98)
Influenza A/H3N2 0.87 (0.78, 0.97)
Influenza B/Austria 0.89 (0.81, 0.98)
Influenza B/Phuket 0.95 (0.87, 1.03)
RSV-A 0.63 (0.57, 0.69)
RSV-B 0.64 (0.58, 0.70)Study 304
0 0.2 0.4 0.6 0.8 1 1.2
GMR (95% CI)11
GMR for all influenza strains close to 1; RSV GMRs lower, potential for clinical impact on efficacy will
be discussed
© 2024 Moderna, inc. All rights reserved.
Correlation of Protection Suggests RSV Vaccine Efficacy Maintained
with Concomitant Administration of mRNA -1345 and Fluzone HD
Study 304 – Adults ≥65 Years
No statistical difference in predicted vaccine efficacy; point estimates were similarAntibody Treatment Group1 Day 22 GMT RSV-LRTD 2+ RSV-LRTD 3+
RSV-A
(IU/mL)Coadministration 11,57070%
(54, 84)86%
(70, 96)
Sequential Administration 19,20377%
(64, 87)88%
(75, 97)
RSV-B
(IU/mL)Coadministration 4,03669%
(51, 83)86%
(69, 97)
Sequential Administration 6,87673%
(58, 85)88%
(73, 97)
1. Concomitant administration: Fluzone HD + mRNA -1345 at Day 1; Sequential Administration: Fluzone HD + placebo at Day 1, mRNA -1345 at Day 22
Correlate of protection model based on ≥ 65 yr olds in study 301 to be consistent with age of study 304 participants 0% 20% 40% 60% 80% 100% 0% 20% 40% 60% 80% 100%
Predicted Vaccine Efficacy
(95% CI)Predicted Vaccine Efficacy
(95% CI)12
© 2024 Moderna, inc. All rights reserved.
Concomitant Administration of mRNA -1345 and Fluzone HD
Well Tolerated with No Safety Concerns Identified
•Concomitant administration well tolerated
•Predominantly mild events
•1-3 days duration
•Reassuring safety profile:
•No Guillain -Barre Syndrome (GBS)
•No acute disseminated encephalomyelitis (ADEM)
•No anaphylaxis
•No thrombocytopenia
•No cases of acute myocarditis or acute pericarditis Study 304
CEAC – Cardiac Event Adjudication Committee13
© 2024 Moderna, inc. All rights reserved.
Concomitant Administration of
mRNA -1345 with Standard Dose
Influenza and COVID -19
Vaccines
Study 302, Parts A & B14
© 2024 Moderna, inc. All rights reserved.
Antibody GMR (95% CI)
Influenza A/H1N1 0.89 (0.77, 1.03)
Influenza A/H3N2 0.97 (0.86, 1.09)
Influenza B/Phuket 0.91 (0.81, 1.02)
Influenza B/Washington 0.93 (0.82, 1.05)
RSV-A Neutralizing 0.81 (0.67, 0.97)
RSV-B Neutralizing 0.85 (0.73, 1.00)Comparable Immunogenicity with Concomitant vs Nonconcomitant
Administration of mRNA -1345 and Standard Dose Influenza Vaccine
Study 302, Part A
0 0.2 0.4 0.6 0.8 1 1.2
GMR (95% CI)15
© 2024 Moderna, inc. All rights reserved.
Comparable Immunogenicity with Concomitant vs Nonconcomitant
Administration of mRNA -1345 and COVID -19 Bivalent Vaccine
Study 302, Part B
Antibody GMR (95% CI)
COVID -19 (Wuhan) 0.96 (0.87, 1.06)
COVID -19 (Omicron) 1.00 (0.89, 1.14)
RSV-A Neutralizing 0.80 (0.70, 0.90)
RSV-B Neutralizing 0.89 (0.79, 1.00)
0 0.2 0.4 0.6 0.8 1 1.2
GMR (95% CI)16
© 2024 Moderna, inc. All rights reserved.
Summary17
© 2024 Moderna, inc. All rights reserved.
Summary of Today’s Presentation18
1. ACIP, Feb 2024 Study 302 Parts A & B – Supports coadministration of mRNA -1345 with standard dose influenza and
COVID -19 vaccines (previously presented)1
•Well tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains, COVID -19, and RSV
Study 304 – Data for coadministration of mRNA -1345 with high -dose influenza vaccine
•Well-tolerated with no safety concerns
•Robust immunogenicity observed for all influenza strains and RSV
•RSV titers lower with coadministration; data from correlate of protection model demonstrate
that clinical efficacy against RSV disease, including severe disease, is likely maintained
Overall, the benefit: risk of coadministration of mRNA -1345 with standard and high -dose influenza
vaccines, and COVID -19 vaccine is positive
Thank you
© 2024 Moderna, inc. All rights reserved.19•Investigators
•Study site personnel
•Laboratory personnel
•Most importantly, the individuals who participated in these trials19