FDA Rejects Moderna’s mRNA Flu Vaccine Application in Unexpected Setback

The U.S. Food and Drug Administration has declined to review Moderna’s application for a new influenza vaccine using mRNA technology, potentially delaying the introduction of a shot designed to provide enhanced protection for older adults and those with underlying health conditions.

Moderna announced Tuesday it had received a “refusal-to-file” (RTF) letter from the FDA’s Center for Biologics Evaluation and Research (CBER), citing concerns about the company’s Phase 3 clinical trial design. According to the FDA, the trial lacked an “adequate and well-controlled” study with a comparator arm that “reflects the best-available standard of care.”

The decision marks a significant setback for Moderna, which has been working to expand its mRNA platform beyond COVID-19 vaccines. Stéphane Bancel, Moderna’s CEO, expressed frustration with the FDA’s decision, stating it “does not further our shared goal of enhancing America’s leadership in developing innovative medicines.”

“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,” Bancel said in a statement.

At the heart of the dispute is Moderna’s choice of comparator vaccine in its Phase 3 trial. The company selected a licensed standard-dose seasonal flu vaccine as its benchmark, which the FDA now says does not represent the “best-available standard of care.” Moderna contends this contradicts previous FDA guidance from 2024 indicating that a standard-dose comparator would be acceptable, though a higher-dose vaccine was recommended for participants over 65.

The pharmaceutical company maintains that the FDA “did not raise any objections or clinical hold comments about the adequacy of the Phase 3 trial” either when the protocol was submitted in April 2024 or before the study began in September 2024. Moderna also stated that the RTF letter did not identify any safety or efficacy concerns with the actual vaccine product.

This rare regulatory action comes amid broader shifts in vaccine policy under Health Secretary Robert F. Kennedy Jr., who has been openly critical of mRNA vaccines and has implemented several policy changes since taking office. Kennedy has removed members from federal vaccine advisory panels, appointed new members, moved to cancel $500 million in mRNA vaccine contracts, and restricted COVID-19 vaccine recommendations to high-risk groups only.

In May, Kennedy announced that COVID-19 vaccines would be removed from the CDC’s routine immunization schedule for healthy children and pregnant women, signaling a significant departure from previous public health approaches.

The timing and nature of the FDA’s decision have raised questions about whether shifting political attitudes toward mRNA technology may be influencing regulatory decisions. However, the FDA has focused its rejection specifically on technical aspects of the trial design rather than on broader concerns about mRNA technology itself.

Moderna says it has requested a Type A meeting with CBER to better understand the basis for the refusal letter and determine a path forward. The company noted that regulatory reviews are continuing in other markets, including the European Union, Canada, and Australia.

The development of mRNA-based influenza vaccines represents an important potential advancement in vaccine technology. Traditional flu vaccines typically offer 40-60% effectiveness, with protection often lower among older adults. Proponents believe mRNA technology could provide more consistent and robust protection against seasonal influenza, which causes between 140,000 and 710,000 hospitalizations annually in the United States.

As Moderna seeks clarity on the FDA’s position, the company faces uncertainty about the timeline for potentially bringing its mRNA flu vaccine to the U.S. market. The outcome of this regulatory dispute could have significant implications not only for Moderna but for the broader development of next-generation vaccine technologies in the United States.