FDA refuses to accept Moderna application for mRNA flu vaccine

The Food and Drug Administration has declined to accept Moderna’s application seeking approval of an mRNA seasonal influenza vaccine, saying the company’s pivotal trial did not use a comparator that reflected the “best‑available standard of care,” according to a letter signed by the agency’s vaccine director.

Moderna announced on Feb. 10 that it had received a refusal-to-file letter from the FDA’s Center for Biologics Evaluation and Research, and posted the letter online. CNN reported the letter was dated Feb. 3 and signed by CBER Director Dr. Vinay Prasad. The agency concluded the filing did not contain an “adequate and well‑controlled trial” because the control arm did not reflect the best-available standard of care in the United States at the time of the study, language cited in multiple summaries of the letter.

The company’s application covered a late-stage study of roughly 40,000 participants that compared Moderna’s mRNA candidate to a standard-dose licensed seasonal influenza vaccine. Moderna said it had also submitted data from a separate trial comparing the candidate against a licensed high-dose shot commonly used in seniors and that the primary trial showed the new vaccine was “somewhat more effective in adults 50 and older” than the standard shot.

Moderna characterized the refusal as procedural, saying the FDA “did not identify any safety or efficacy concerns with our product.” Stéphane Bancel, Moderna’s chief executive, said the decision “does not further our shared goal of enhancing America’s leadership in developing innovative medicines,” language the company included in its public statement. Moderna president Dr. Stephen Hoge told CNN that “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,” reflecting the company’s contention that earlier feedback permitted its trial design.

The dispute hinges on whether Moderna followed written guidance the company says it received from the FDA in 2024. Moderna maintains that agency feedback at the time allowed the use of a standard-dose comparator, while noting the FDA had advised a higher-dose vaccine would be preferred for participants 65 and older. The RTF letter, by contrast, referenced 2024 advice that Moderna did not follow, according to the text cited by regulators in the letter.

Moderna has requested a meeting with FDA officials to clarify next steps and to determine how it might address the agency’s concerns. The refusal-to-file prevents the FDA from initiating a formal review until Moderna supplies additional information or amends the application to meet regulatory requirements.

The action immediately raises questions about the timetable for bringing an mRNA-based flu vaccine to market, especially for older adults who receive different formulations from standard-dose shots. Some commentators and outlets have linked the decision to heightened scrutiny of mRNA vaccines under Health Secretary Robert F. Kennedy Jr., a narrative advanced in coverage noting recent policy shifts and reassessments of vaccine recommendations at the federal level.

Regulatory experts say comparator selection in large Phase 3 vaccine trials is critical because it determines whether effectiveness can be judged against the real-world standard of care, and a finding that a trial is not well controlled can require new studies or additional analyses. Moderna’s next steps are likely to include negotiations with the agency about acceptable comparators and whether the submitted high-dose data can address the RTF’s core concerns.