FDA Data on Moderna’s 2 RSV Vaccines for Infants Raise Safety Concerns
The federal agency stated there were cases of RSV lower respiratory tract infection (LRTI) post-immunization for 2 of the company’s vaccines, mRNA-1345 and mRNA-1365.
Image credit: FDA
Ahead of its Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting tomorrow, the FDA released data in its briefing document looking at RSV vaccines and specifically discussed Moderna’s mRNA RSV vaccines, mRNA-1345 and mRNA-1365, detailing cases of RSV LRTI post-immunization.1
Back in July, Moderna informed the FDA of a potential safety signal for RSV severe LRTI that was identified (Table 1).1
“An imbalance in severe RSV LRTI was noted following administration of mRNA-1345 and mRNA-1365 vaccine candidates to infants,” the FDA briefing stated.1 This later evolved into Moderna pausing the study altogether and the FDA putting a clinical hold on the program.1
According to 1 news report, Moderna paused the study of mRNA-1345 for infants back in September.2
In addition, Moderna informed FDA of human metapneumovirus (hMPV) cases around the mRNA-1365, which was being developed as a combination vaccine for both RSV and hMPV immunization. “On November 22, 2024, sponsor provided updated information on cases of hMPV hospitalizations in their cohorts 3 and 4. Two were vaccine recipients (Cohort 4, mRNA-1365), including one participant who required non-invasive positive pressure ventilation and one was a placebo recipient with a co-infection with RSV. Additional clinical and immunologic data are currently not available,” the FDA authors wrote.1
Table 1 credit: FDA
mRNA-1345 and Nirsevimab
Additionally, the document included information detailing the effects of 1 of the vaccines, mRNA-1345, after previous treatment with nirsevimab-alip (Beyfortus) (Table 2).1 “These results suggest a potential lack of response to a single dose of mRNA-1345 (30 μg) when administered to individuals previously exposed to nirsevimab, most notably for post-dose 1 RSV B GMT (249 IU/mL) in nirsevimab-exposed compared with post-dose 1 RSV B GMT (1678 IU/mL) in nirsevimab-unexposed participants. Antibody responses following the 3-dose series are not available because participants did not receive additional doses due to the study pause.”1
Table 2. RSV A and RSV B Neutralizing Antibody (nAb) Responses Based on RSV Infection Classification, 5 Months – <8 Months of Age, Study mRNA-1365-P101,
Part B Cohorts 3 and 4
Table credit: FDA
What Does This Mean Going Forward?
The FDA authors say there is uncertainty with these types of vaccines, especially as concerns around potential adverse effects of vaccine-associated enhanced respiratory disease (VAERD) arise. “The observed imbalance in severe/very severe cases of RSV LRTI in the mRNA-1345 and mRNA-1365 vaccine development program among 5-month to <8-month-old recipients of mRNA-1345 (15 μg) and mRNA-1365 (15 μg) has uncertain implications for the ongoing and future pediatric development of other non-live attenuated RSV vaccines,” the authors wrote.1
The FDA says that with the existing data around both Moderna vaccines, the decision to reinitiate enrollment of at-risk populations for VAERD and move forward with studies of other non-live attenuated RSV vaccines in the pediatric population will need to consider 7 aspects including around vaccine safety and data to identify the risk and benefit.1
According to the VRBPAC agenda for Thursday's meeting, there is a good portion of the meeting dedicated to discussing RSV vaccines and this ongoing issue. However, there is no specific vote set-up to provide specific guidance or recommendations for the future of these types of vaccines in the pediatric population.
To view the meeting briefing document, interested readers can go here.
