FDA refuses to file Moderna’s mRNA influenza vaccine application

The U.S. Food and Drug Administration has declined to initiate review of Moderna’s biologics license application for its investigational mRNA influenza vaccine, mRNA-1010, issuing a Refusal-to-File (RTF) letter that centers on trial design rather than safety or efficacy concerns, the company announced.

According to Moderna, the FDA’s Center for Biologics Evaluation and Research (CBER) determined that a Phase 3 efficacy study comparing the investigational vaccine with a licensed standard-dose influenza vaccine did not meet expectations for an “adequate and well-controlled” study because the comparator “does not reflect the best-available standard of care.” The agency did not cite specific safety or effectiveness issues with the vaccine candidate.

Moderna said the decision conflicts with earlier agency communications. In a 2024 pre-Phase 3 consultation, CBER indicated that use of a licensed standard-dose influenza vaccine comparator would be acceptable, though it recommended using vaccines preferentially recommended for adults older than 65 years in that population. The company reported that FDA reviewers did not object to the Phase 3 design before study initiation in September 2024.

In a statement, CEO Stéphane Bancel said the refusal “did not identify any safety or efficacy concerns with our product” and added that the company plans to work with regulators “to understand the path forward as quickly as possible.”

Moderna has requested a Type A meeting with CBER to discuss the decision. The company said it does not expect the RTF to affect its 2026 financial guidance.

The mRNA-1010 application was supported by two Phase 3 studies involving more than 43,000 participants. One trial compared the vaccine with a high-dose influenza vaccine in adults aged 65 years or older, while another evaluated safety and relative efficacy against a licensed standard-dose influenza vaccine in adults aged 50 years or older. Moderna reported that both trials met prespecified primary endpoints and showed statistical superiority over their respective comparators.

Regulatory reviews of mRNA-1010 are ongoing in the European Union, Canada and Australia, with potential approvals in those regions anticipated beginning in late 2026 or early 2027, pending regulatory decisions.