FDA refuses to review Moderna’s mRNA seasonal flu vaccine application

The U.S. Food and Drug Administration notified Moderna that it will not initiate review of the company’s biologics license application for mRNA-1010, an investigational mRNA seasonal influenza vaccine, because the pivotal trials compared the candidate to a licensed standard-dose shot rather than what the agency described as the best-available standard of care. The refusal-to-file letter, dated Feb. 3 and signed by the director of the agency’s Center for Biologics Evaluation and Research, Vinayak Prasad, MD, MPH (also referenced as Dr. Vinay Prasad), was disclosed by Moderna in a Feb. 10 announcement.

The agency’s letter said the submission “did not contain an ‘adequate and well-controlled’ trial” because the control arm “does not reflect the best-available standard of care.” The communication did not identify specific safety or efficacy concerns with mRNA-1010, company officials have said. Moderna has requested a meeting with CBER to “understand the path forward” and asked for clarification of the agency’s position.

Moderna’s briefing materials and prior public statements say the BLA included two late-stage studies, one enrolling more than 40,000 participants, and that the candidate showed stronger performance than an FDA-approved annual flu shot. The company previously reported that mRNA-1010 was 26.6 percent more effective than an approved comparator from GSK. In the trials, Moderna used Fluarix as the standard-dose comparator, according to the company’s disclosures.

Moderna executives pushed back on the FDA’s decision. Chief executive Stéphane Bancel said, “It should not be controversial to conduct a comprehensive review of a flu vaccine submission that uses an FDA-approved vaccine as a comparator in a study that was discussed and agreed on with CBER prior to starting.” President Stephen Hoge added, “The complete stunner here is at no point in any of this did anybody say that it was not adequate” to run its clinical trial the way it had discussed with the agency.

The company also said it had exercised a Priority Review Voucher for the U.S. filing, requested a Type A meeting to resolve the dispute, and expects no impact on its 2026 financial guidance. Moderna noted the application has been submitted and accepted for review in the European Union, Canada and Australia.

The regulatory disagreement has immediate market consequences. Shares of Moderna fell in extended trading after the announcement, and closed the regular session at $41.99, with the company’s stock down materially in after-hours transactions.

The procedural rationale cited by CBER highlights a broader debate over acceptable comparators in vaccine trials. Moderna and outside legal observers point out that the quoted regulatory text, 21 C.F.R. § 314.126, and FDA guidance on seasonal influenza vaccines do not explicitly reference a “best-available standard of care” comparator requirement. Former FDA chief scientist Jesse Goodman, now at Georgetown University, cautioned that abrupt shifts in agency expectations would be unusual, saying, “What’s unusual here is if they sort of move the goalposts and said one thing ... almost two years ago before this started, and then to change that without some major new science or concern coming up.”

Moderna has asked CBER for a prompt meeting; the company and regulators now face a decision that will shape not only the timetable for a potential U.S. flu mRNA vaccine but also precedent on how comparator choices are judged in future vaccine approvals.