Following news of RSV lower respiratory tract infections in infants immunized with Moderna’s investigational RNA vaccines, FDA advisors said the trial investigators should continue the study, while keeping an eye out for further safety signals.
An FDA advisory committee reviewing an imbalance in severe respiratory syncytial virus cases in a trial of Moderna’s vaccine has urged the FDA and companies to continue the research—albeit carefully.
The Vaccines and Related Biological Products Advisory Committee met Thursday to discuss safety findings for mRNA-1345 and mRNA-1365. The FDA flagged an imbalance in severe cases of RSV in infants who received the shot and a possible “blunting” effect of antiviral treatment in those who had received the vaccine. The committee did not vote on a course of action but discussed the implications of the safety findings.
During the meeting, experts said there was not enough information and that more investigation is needed to determine if the safety signal is indeed real. Companies should therefore proceed—cautiously—with clinical trials in infants rather than halting research and never finding an answer.
Original story published Dec. 11:
Moderna’s RSV Vaccines Run Into Safety Roadblock
The FDA on Tuesday revealed that it has detected severe side effects in two of Moderna’s experimental mRNA-based respiratory syncytial vaccine candidates, which the biotech is advancing for the immunization of infants.
In a briefing document released ahead of an advisory committee meeting later this week, the regulator’s staffers flagged “an imbalance in severe RSV [lower respiratory tract infection (LRTI)]” in infants given Moderna’s investigational mRNA-1345 and mRNA-1365 shots. Additionally, the report noted that the responses to prophylactic antibody Beyfortus (nirsevimab) were “blunted” after vaccination with the mRNA shots.
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will convene on Thursday to discuss these safety findings for mRNA-1345 and mRNA-1365—though no vote will be held. The panelists will determine “the implications of these findings for ongoing and future pediatric development of other non-live attenuated RSV vaccines,” as well as the potential interactions between RSV prophylactic antibodies and vaccines.
Moderna’s mRNA-1345 won the FDA’s approval in May for use in adults aged 60 years and above, and is being marketed under the brand name mRESVIA. The company was also previously developing the shot for use in infants, but dropped this program in September, according to reporting by Endpoints News. According to the biotech’s website, mRNA-1345 continues to move forward in high-risk adults aged 18 to 59 years, and in a pediatric population.
Meanwhile, mRNA-1365 is being developed as a combination vaccine for RSV and the human metapneumovirus. The candidate is currently in a Phase I study in this indication.
In its briefing document, the FDA revealed that in one study, inoculation with mRNA-1365 led to a case of severe or very severe RSV LRTI in the subgroup of participants aged 8 months to less than 24 months. In a younger subpopulation—aged 5 months to less than 8 months—five such side effects were reported after mRNA-1635 administration.
Moderna was made aware that there were at least two positive RSV LRTI tests in the study by July 17, triggering one of the study’s pause criterion. A few days later, Moderna enacted a “study-wide pause,” according to the briefing document, amid its ongoing safety investigation.
These new safety data come as a blow to Moderna, which was already struggling to find its footing in the RSV vaccine space, where it is in third place. GSK became the frontrunner in this field when it won the FDA’s first approval in May 2023 for Arexvy, which has since gone on to corner around two-thirds of all retail RSV vaccinations in the U.S.
Pfizer has fallen to second place with its Abrysvo, though recent approvals in a broader adult population and in immunocompromised adults could help the pharma shore up sales for its shot.
Correction (Dec. 11): This story has been updated to make it clear that Moderna informed the FDA of the safety findings that triggered the study pause, not the other way around. BioSpace regrets the error.
