U.S. rejects Moderna’s mRNA vaccine application, cites trial design concerns

The U.S. Food and Drug Administration (FDA) has declined to review Moderna’s application for its experimental mRNA-based influenza vaccine, mRNA-1010, in a move that industry observers describe as highly unusual and potentially indicative of a tougher regulatory climate for vaccine approvals.

In a Feb. 3 “refusal-to-file” letter signed by Dr. Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research, the agency cited what it described as the company’s failure to conduct an “adequate and well-controlled” clinical trial and to apply the “best-available standard of care” during the study.

Moderna disclosed the letter publicly on Tuesday.

According to Bloomberg L.P., the FDA rarely issues refusal-to-file letters. A 2021 study published in JAMA Internal Medicine found that only 4% of 2,475 applications reviewed by the agency resulted in such a response. The decision signals what Bloomberg described as a “new aggressive phase” in federal drug regulation, with heightened demands for rigorous clinical data.

The development follows reports by The Washington Post that federal regulators have adopted a stricter posture toward vaccine approvals in recent months.

Moderna’s Phase 3 trial enrolled more than 43,000 participants aged 50 and older. Rather than comparing the mRNA-1010 vaccine to a placebo, the company tested it against existing flu vaccines. In one study arm, participants received either the experimental shot or a standard-dose influenza vaccine.

In another, participants were given the mRNA vaccine, a standard-dose shot, or a high-dose influenza vaccine recommended for adults 65 and older.

In a statement cited by Fierce Biotech, FDA Commissioner Marty Makary criticized the trial design, alleging that seniors were exposed to unnecessary risk.

“Moderna exposed participants age 65 and over to increased risk of severe illness by giving them a substandard of care against the recommendations of FDA career scientists,” Makary said.

However, reporting by STAT suggested that Prasad overruled senior FDA vaccine reviewers who had been prepared to evaluate the application. Andrew Nixon, spokesperson for the U.S. Department of Health and Human Services, told STAT that claims of internal disagreement were “categorically false.”

In a company statement, Moderna CEO Stéphane Bancel said the agency’s action “does not further our shared goal of enhancing America’s leadership in developing innovative medicines.” He emphasized that the FDA’s letter did not cite any specific safety or efficacy deficiencies in the vaccine itself.

If ultimately approved, mRNA-1010 would become the first licensed mRNA-based influenza vaccine in the United States.

READ ALSO: Mercedes-Benz Records Lowest Profit Since COVID-19 Pandemic

Questions Over Safety and Effectiveness

Some independent experts have raised concerns about the trial data. Pharmacologist Maria Gutschi described the FDA’s move as potentially reflecting “appropriate regulatory caution,” citing what she characterized as concerning safety signals, including higher reported rates of certain adverse outcomes.

The trial reported a relative vaccine efficacy of 26.6%. Critics have contrasted this figure with the higher relative efficacy reported for mRNA COVID-19 vaccines during earlier trials. Analysts note, however, that relative efficacy measures differ depending on study design and comparator vaccines used.

The distinction between relative and absolute vaccine effectiveness has also been part of the debate. Relative effectiveness compares different vaccines or dosing regimens, while absolute effectiveness compares vaccinated and unvaccinated groups.

Financial markets reacted swiftly to the news. Moderna’s shares fell 8% in extended trading following disclosure of the FDA’s decision. Despite a 42% rise earlier this year, the company’s stock remains more than 90% below its 2021 peak, according to Bloomberg.

In 2024, Moderna secured $750 million in private equity funding from Blackstone Life Sciences to support the development and clinical testing of mRNA-1010.

The FDA’s decision comes amid indications of a broader reassessment of vaccine oversight. A leaked November 2025 memo reportedly outlined plans to revise how annual flu shot formulations are evaluated. Separately, in June 2025, the Centers for Disease Control and Prevention updated its guidance on certain flu vaccine components.