The U.S. Food and Drug Administration will not begin a review of Moderna's application seeking approval for its influenza vaccine candidate mRNA-1010, the company said on Tuesday. The announcement followed receipt of a refusal-to-file letter in which the agency identified the trial comparator choice as the sole reason for declining to initiate a formal review.
According to Moderna, the letter from the FDA's Center for Biologics Evaluation and Research (CBER) took issue with the design of the studies submitted in support of the application. The regulator told the company there was a lack of an "adequate and well-controlled" study that included a comparator arm that "does not reflect the best-available standard of care," Moderna said.
The company emphasized that CBER's decision did not raise any safety or efficacy concerns about mRNA-1010. In a statement, Moderna's chief executive, Stephane Bancel, said: "This decision by CBER (Center for Biologics Evaluation and Research), which did not identify any safety or efficacy concerns with our product, does not further our shared goal of enhancing America’s leadership in developing innovative medicines."
Bancel also described the regulator's position as inconsistent with earlier written communications, noting that the study design used an FDA-approved comparator that had been discussed with CBER prior to trial commencement. He added: "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."
Moderna's filing included data from two late-stage studies, which the company says met the primary goals of the trials. The company previously reported that its mRNA-1010 candidate showed a 26.6% improvement in effectiveness compared with an approved annual influenza vaccine produced by GSK.
Following the FDA's refusal-to-file, Moderna's shares fell about 8% in extended trading. The company has asked for a meeting with the regulator to seek clarity on a path forward, the statement said.
The regulatory setback arrives in a broader environment of shifting U.S. immunization policy. The development was disclosed shortly after the United States revised its guidance on childhood immunization, rolling back routine vaccination recommendations for six infectious diseases, including influenza.
Moderna previously withdrew a separate application seeking approval for a combined influenza and COVID-19 vaccine, electing to wait for efficacy results from the late-stage trial of its influenza-only candidate. The company has also indicated it does not plan to invest in new late-stage vaccine trials in the near term, citing growing opposition to immunizations from some U.S. officials.
Outside the United States, Moderna's influenza vaccine is under regulatory review in the European Union, Canada and Australia. The company has forecast the potential for approvals in those jurisdictions in late 2026 or early 2027. Current FDA-approved influenza vaccines are produced by companies including AstraZeneca and Sanofi.
Context and next steps
Moderna has requested a meeting with CBER to better understand the regulator's assessment and determine what, if any, adjustments to the submission or trial data could enable a future filing. The company maintains that the late-stage studies submitted met their primary endpoints and that the choice of comparator was arranged with the regulator before the trials began.
This regulatory decision halts the initiation of a formal review in the United States while other jurisdictions continue their own assessments.