WASHINGTON: The U.S. Food and Drug Administration has declined to accept for review Moderna’s application to license its seasonal influenza vaccine candidate mRNA-1010, issuing a refusal-to-file letter that stops the agency’s formal review process at the filing stage. Moderna said the FDA’s Center for Biologics Evaluation and Research sent the notice on Feb. 3, and the company disclosed the decision on Feb. 10. Moderna shares fell about 8% in after-hours trading after the disclosure.
Moderna said the refusal-to-file letter cited a single issue, the choice of comparator used in a pivotal late-stage study, and did not raise safety or effectiveness concerns about mRNA-1010. The company said the letter, signed by CBER Director Vinayak Prasad, stated the evidence package lacked an adequate and well-controlled study because the comparator arm did not reflect what the agency described as the best-available standard of care for the population studied.
The dispute centers on whether Moderna’s main efficacy trial should have compared mRNA-1010 against influenza vaccines commonly preferred for older adults, rather than a licensed standard-dose flu shot. Moderna’s filing relied in part on a study in adults 50 years and older that compared mRNA-1010 with a standard-dose vaccine comparator, which Moderna identified as Fluarix, a product of the GlaxoSmithKline group of companies.
Moderna said it used a priority review voucher to seek an accelerated review timetable for the application and has requested a Type A meeting with CBER, a formal meeting category used for addressing stalled development or review issues. Moderna also said it posted the full refusal-to-file letter online. The company described the filing decision as inconsistent with prior written feedback it received from the regulator during trial planning and pre-submission discussions.
Comparator choice and trial design
In its Feb. 10 disclosure, Moderna said its biologics license application included two Phase 3 studies enrolling a total of 43,808 participants and meeting all pre-specified primary endpoints. Moderna said P304 was a safety and relative efficacy study comparing mRNA-1010 with a licensed standard-dose influenza vaccine in adults 50 years and older. Moderna said P303 Part C was a safety and immunogenicity study in adults 65 years and older that compared mRNA-1010 with a licensed high-dose influenza vaccine.
Moderna said CBER reviewed the Phase 3 study protocol before trial initiation and provided written feedback in April 2024 stating it would be acceptable to use a licensed standard-dose influenza vaccine as the comparator, while recommending a vaccine preferentially recommended for older adults for participants older than 65 years. Moderna said the regulator also agreed with the company’s plan to include specific statements in the informed-consent form if a standard-dose comparator was used in participants older than 65, and that the agency did not place the trial on clinical hold before enrollment began in September 2024.
Moderna said it held a pre-submission meeting with CBER in August 2025 after the efficacy study met its agreed primary endpoints. Moderna said CBER requested supportive analyses related to the comparator and indicated the issue would be significant during review. Moderna said it included the requested analyses in its submission, including data from the separate Phase 3 study comparing mRNA-1010 with a high-dose influenza vaccine in adults 65 and older, and that CBER did not indicate it would refuse to file the application.
Influenza vaccine standards and filing process
U.S. public-health guidance for older adults has increasingly emphasized enhanced influenza vaccine options. The Centers for Disease Control and Prevention’s ACIP recommendation summary states that adults aged 65 years and older should preferentially receive either a high-dose inactivated influenza vaccine, a recombinant influenza vaccine, or an adjuvanted inactivated influenza vaccine when those options are available. The ACIP summary states that if none of the preferred options is available at a vaccination opportunity, any other age-appropriate influenza vaccine should be used.
A refusal-to-file decision means the FDA will not accept an application as filed and will not start a substantive review under the standard licensing timeline. FDA procedures describe refusal-to-file as a threshold determination used when deficiencies are significant enough to prevent a prompt and meaningful review, and as distinct from a complete response decision issued after a full review cycle. Moderna said mRNA-1010 has been accepted for review by regulators in the European Union, Canada, and Australia. – By Content Syndication Services.