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Maternal & Pediatric RSV Work Group Interpretations
and Next Steps
Danielle Moulia, MPH
Co-Lead, Maternal/Pediatric RSV Work Group
ACIP Meeting
October 23, 2024
1U.S. Centers for Disease Control and Prevention
Safety and efficacy of clesrovimab
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Policy question being considered by the work group
•Should clesrovimab be recommended for all infants <8 months of age
entering their first RSV season or born during the RSV season?
3
Evidence reviewed by the work group
•Safety and efficacy of clesrovimab
-Phase 2b/3 placebo -controlled study in healthy preterm infants (≥29
to <35 weeks gestational age) and full -term infants (≥35 weeks
gestational age)
-Phase 3 palivizumab -controlled study in infants at increased risk for
severe RSV disease
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Work group interpretation of clesrovimab efficacy
data
•Phase 2b/3 trial demonstrated high efficacy for prevention of severe RSV
disease through 150 days
*Defined by the presence of the following: cough or difficulty breathing; AND ≥ 1 indicator of LRI (lower respiratory infecti on) or severity (wheezing, chest wall in -
drawing/retractions, rales/crackles, hypoxemia, tachypnea, dehydration due to respiratory symptoms ); AND hospital admission for respiratory illness; AND RSV
positive reverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample.
**Defined by the presence of the following seen in an outpatient or inpatient clinical setting: cough or difficulty breathing and ≥ 1 indicator of (lower respiratory
infection) or severity (wheezing, chest wall in -drawing/retractions, rales/crackles, hypoxemia, tachypnea, dehydration due to respiratory s ymptoms); and RSV positive
reverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample.
5Outcome n/N, clesrovimab n/N, placebo Efficacy % (95% CI)
Hospitalization for RSV-
associated lower respiratory
tract infection*5/2,398 27/1,201 90.9 (76.2, 96.5)
Medically -attended RSV-
associated lower respiratory
tract infection ≥ 1 indicator of
lower respiratory infection or
severity**60/2,398 74/1,201 60.4 (44.1, 71.9)
Merck, presented at IDWeek in Los Angeles, California from October 16 -19, 2024
Work group interpretation of clesrovimab safety data
•Serious adverse events appeared balanced between the clesrovimab and
placebo arms, however rare adverse events are unlikely to be detected in a
trial of this size
•Solicited adverse events were balanced between the clesrovimab and
placebo arms
-In both arms, irritability and sleepiness was the most commonly observed
solicited adverse event
6 Merck, presented at IDWeek in Los Angeles, California from October 16 -19, 2024
Work group considerations regarding clesrovimab
•Initial efficacy and safety data look promising; however, the work group has
requested additional pharmacokinetic, efficacy, and safety data from the
manufacturer
•Work group discussion also highlighted:
-Clesrovimab has demonstrated a shorter half -life than nirsevimab (421 vs 712 days), however
efficacy against severe RSV appeared sustained at 150 and 180 days
-Trial enrollment began in 2021, a period when typical RSV seasonality had been disrupted by the
COVID -19 pandemic
-Clesrovimab and nirsevimab trial outcomes had different definitions
•Overall, the work group felt that the initial data merited moving forward
with the evidence review for the policy question
1 Maas et al. https://www.sciensano.be/sites/default/files/pk_sna_and_efficacy_against_rsv_malri_from_a_phase_1b2a_study_of_the_monoclonal_ antibody_clesrovimab_mk -
1654_in_infants.pdf 2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf 7
Evidence to be reviewed by the work group
•Additional data on Phase 2b/3 and Phase 3 studies requested by work
group
•GRADE of evidence
•Cost effectiveness analysis
•Evidence to Recommendation Framework ( EtR)
-Public health problem
-Benefits and harms
-Values
-Acceptability
8-Feasibility
-Resource use
-Equity
Proposed timeline
•February 2025
-Summary of GRADE
-Evidence to Recommendation Framework
-Cost effectiveness analysis
•ACIP vote timing dependent on FDA licensure
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Maternal RSV vaccine safety
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Imbalance of preterm birth was observed in clinical
trials for the Pfizer maternal RSV vaccine ( Abrysvo )
•In clinical trials, maternal RSV vaccine was administered at 24 –36 weeks' gestation,
and more preterm births and hypertensive disorders of pregnancy were observed
among pregnant people who received maternal RSV vaccine ( Abrysvo )vs. placebo,
but the differences were not statistically significant
– Data were insufficient to establish or exclude a causal relationship
•FDA approved maternal RSV vaccine ( Abrysvo ) for use in pregnant persons at 32 –36
weeks’ gestation to avoid the potential risk for preterm birth at <32 weeks’ gestation
•ACIP judged the benefits of maternal RSV vaccine ( Abrysvo ) at 32 –36 weeks’
gestation to outweigh the potential risks for preterm birth and hypertensive
disorders of pregnancy
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Maternal RSV vaccine safety: first season analysis of
preterm birth and small for gestational age
•Preliminary findings from the first season of maternal RSV vaccine in a Vaccine Safety Datalink
(VSD) study found that maternal RSV vaccine during 32 –36 weeks’ gestation was not
associated with an increased risk of preterm birth or small for gestational age1
•The work group felt that these data were very reassuring.
1. DeSilva, M. RSVpreF Vaccine, Preterm Birth, and Small for Gestational Age at Birth Preliminary Results from The Vaccine Safety Datalink. Presented at ACIP October 23, 2024 2. Talge NM, Mudd LM, Sikorskii
A, Basso O. United States birth weight reference corrected for implausible gestational age estimates. Pediatrics 2014;133:844 53. PMID:2477721612Matched
pairs, NRSV vaccinated Unvaccinated matchRisk Ratio (95%
CI)
N events* Percent % N events* Percent %
Preterm birtha13,965 563 4.0 628 4.50.90
(0.80 –1.00)
Small for gestational ageb11,819 799 6.8 774 6.51.03
(0.94 –1.14)
aPreterm birth = birth <37 weeks gestational age bSGA at birth = “Small for Gestational Age”; birthweight <10th percentile for gestational age compared with a U.S. reference
population2
*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated
Work group interpretation of maternal RSV vaccine
safety data
•The work group felt that messaging about potential risks for hypertensive disorder
of pregnancy should be separated from preterm birth
•Little post -licensure data available for risk of hypertensive disorder of pregnancy
•One study conducted a secondary analysis of 2,973 pregnant individuals (1,011
vaccinated and 1,962 unvaccinated) found an association of maternal RSV vaccine
and hypertensive disorder of pregnancy1
•Some WG members felt that when counseling pregnant people on maternal RSV
vaccination at 32 –36 weeks, messaging on potential risks of preterm birth could be
softened or counselling no longer needed to include discussion regarding a
potential risk of preterm birth
•CDC and FDA should continue to monitor safety data for maternal RSV vaccine,
including further VSD analyses for hypertensive disorders of pregnancy
131. Son M, Riley LE, Staniczenko AP, et al. Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal Outcomes. JAMA Netw Open. 2024;7(7):e2419268.
doi:10.1001/jamanetworkopen.2024.19268
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