The FDA has declined to review Moderna’s application for an mRNA flu vaccine, citing study design issues, while the company disputes the decision, claiming it contradicts previous guidance.
The U.S. Food and Drug Administration (FDA) has refused to review Moderna’s application for a new flu vaccine utilizing mRNA technology, a decision that may postpone the rollout of a vaccine aimed at providing enhanced protection for older adults. The company announced this development on Tuesday, revealing that it received a “refusal-to-file” (RTF) letter from the FDA’s Center for Biologics Evaluation and Research (CBER).
The FDA’s refusal was based on concerns regarding the study design, specifically the lack of an “adequate and well-controlled” study that included a comparator arm not representative of the best-available standard of care. Stéphane Bancel, Moderna’s chief executive officer, expressed disappointment over the FDA’s decision, emphasizing that it did not cite any safety or efficacy issues with the vaccine.
Bancel stated, “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.” He added that the company is eager to engage with CBER to clarify the path forward, ensuring that seniors and individuals with underlying conditions have access to innovative American-made solutions.
This unusual decision from the FDA comes amid heightened scrutiny over vaccine approvals under Health Secretary Robert F. Kennedy Jr., who has publicly criticized mRNA vaccines and has made changes to COVID-19 vaccination recommendations over the past year. Kennedy has previously removed members from the federal vaccine advisory panel, appointed new members, and sought to cancel $500 million in mRNA vaccine contracts.
Recently, the FDA authorized COVID-19 vaccines for high-risk groups only, and in May, Kennedy announced that these vaccines would be removed from the CDC’s routine immunization schedule for healthy children and pregnant women.
Moderna contends that the refusal-to-file decision stemmed from its choice of comparator in the Phase 3 trial, which involved a licensed standard-dose seasonal flu vaccine. The FDA argued that this choice did not reflect the “best-available standard of care.” However, Moderna maintains that this decision contradicts previous written communications from the FDA, including guidance issued in 2024 that indicated a standard-dose comparator would be acceptable, although a higher-dose vaccine was recommended for participants aged 65 and older.
According to Moderna, the FDA did not raise any objections or clinical hold comments regarding the adequacy of the Phase 3 trial after the submission of the protocol in April 2024 or at any point before the study began in September 2024.
In August 2025, following the completion of the Phase 3 efficacy trial, Moderna held a pre-submission meeting with CBER, during which the agency requested additional analyses regarding the comparator to be included in the submission. CBER indicated that this data would be a “significant issue” during the review of the Biologics License Application (BLA). Moderna asserts that it provided the requested analyses and that CBER did not indicate any intention to refuse to review the file during the pre-submission feedback or meeting.
The company has requested a Type A meeting with CBER to better understand the rationale behind the RTF letter, noting that regulatory reviews are still ongoing in the European Union, Canada, and Australia.
Fox News has reached out to the Department of Health and Human Services for further comment on this matter.
According to Fox News, the situation underscores the complexities surrounding vaccine approvals and the ongoing debates within the health sector regarding mRNA technology.