FDA Rejects Moderna’s mRNA Flu Vaccine Application Despite Positive Trial Data

WASHINGTON — The Food and Drug Administration (FDA) refused to review Moderna’s application for its mRNA-based seasonal flu vaccine, the company announced Tuesday, marking a significant setback for the technology and raising questions about the future of influenza prevention in the United States. The decision, communicated in a “refuse-to-file” letter dated February 3, centers on the design of Moderna’s clinical trial and reflects a growing tension between the agency and the pharmaceutical company.

According to the FDA, the application lacked an “adequate and well-controlled” trial as the control arm – the group receiving the standard flu vaccine for comparison – did not reflect the “best-available standard of care in the United States at the time of the study.” Specifically, the agency faulted Moderna for comparing its vaccine to a standard-dose flu shot, rather than a high-dose vaccine recommended for older adults, who are particularly vulnerable to severe influenza. CNN and USA Today reported on the FDA’s reasoning.

Moderna disputes the FDA’s assessment, stating that the agency’s concerns are inconsistent with previous feedback. The company initiated a Phase 3 trial in 2025 involving over 40,000 participants aged 50 and older, comparing mRNA-1010.6 to the Fluarix vaccine. Moderna maintains it provided the necessary comparison for older populations. “The letter is inconsistent with previous written communications from CBER to Moderna,” the company said in a statement. Dr. Stephen Hoge, Moderna’s president, told CNN that “at no point” did the FDA indicate the trial design was inadequate prior to this refusal.

The FDA’s decision comes amid broader scrutiny of vaccine development and approval processes under the Trump Administration. Secretary of Health and Human Services Robert F. Kennedy Jr. Has overseen significant changes at both the FDA and the Centers for Disease Control and Prevention (CDC), including the removal of expert committee members and revisions to vaccine recommendations. Earlier this year, HHS canceled a $590 million contract with Moderna for an mRNA bird flu vaccine, and Kennedy indicated a shift away from mRNA vaccine development in favor of other platforms.

An FDA spokesperson, Andrew Nixon, countered Moderna’s claims, stating the agency rejected the application because Moderna “refused to follow very clear FDA guidance from 2024 to test its product in a clinical trial against a CDC-recommended [high-dose] flu vaccine to compare safety and efficacy.” Nixon further asserted that Moderna “exposed participants age 65 and over to increased risk of severe illness by giving them a substandard of care against the recommendation of FDA scientists.” Fierce Biotech reported on the HHS defense of the FDA’s decision.

The decision is particularly notable given the potential advantages of mRNA technology in responding to influenza. Traditional flu vaccines, which rely on growing the virus in chicken eggs, require months of lead time to update for circulating strains. MRNA technology, as demonstrated with COVID-19 vaccines, allows for rapid adaptation to new viral variants, potentially offering a more effective and timely response to seasonal flu outbreaks. The World Health Organization typically recommends updated flu strains in the spring, but the lengthy production process for traditional vaccines can limit their effectiveness.

While the FDA review is stalled in the U.S., Moderna is pursuing regulatory approval for mRNA-1010.6 in Europe, Canada, and Australia. The company plans to submit applications in other countries this year, potentially meaning that individuals outside the United States could receive the first mRNA flu shots. According to reporting by AOL, the FDA’s decision could delay access to the new vaccine for Americans.

Adding to the complexity, STAT News reported that Dr. Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research (CBER), made the decision to refuse the filing against the advice of his staff, who were prepared to review the application. This internal disagreement raises further questions about the agency’s rationale and the influence of political considerations on scientific judgment. The outcome of Moderna’s requested meeting with FDA officials remains uncertain, leaving the future of its mRNA flu vaccine in the U.S. Market in limbo.