Moderna has received a refusal-to-file (RTF) letter from the US Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) pertaining to its investigational influenza vaccine, mRNA-1010.
The company had exercised a Priority Review Voucher to facilitate a timely review of the application.
According to Moderna, the letter took umbrage with the choice of a "licensed standard-dose seasonal influenza vaccine" as the trial's control arm.
Specifically, the letter cited the lack of an "adequate and well-controlled" study with a comparator arm that "does not reflect the best-available standard of care."
According to the company, neither federal regulations nor the FDA's own guidance on seasonal influenza vaccines contains any reference to the use of a comparator reflecting the "best-available standard of care."
The letter did not identify any specific safety or efficacy concerns regarding mRNA-1010.
Moderna has said that the letter is "inconsistent with previous written communications from CBER."
The news has thrown into focus the growing anti-mRNA stance within the FDA and Department of Health and Human Services (HHS).
What led up to this?
Moderna submitted the Phase III study protocol to CBER for review in 2024.
CBER provided written guidance noting that "while we agree it would be acceptable to use a licensed standard dose influenza vaccine as the comparator in your Phase III study, we recommend you use a vaccine preferentially recommended for use in older adults by the ACIP (i.e., Fluzone HD, Fluad or Flublok) for participants >65 years of age in the study."
"Data on the comparative efficacy of your vaccine against an influenza vaccine preferentially recommended for use in the >65 years age group may help inform ACIP's recommendation for the use of your vaccine in the older adult population."
"If you proceed with using a standard dose influenza vaccine comparator in participants ≥65 years of age, we agree with your plan to include statements in the Informed Consent Form."
CBER did not raise any objections or clinical hold comments about the adequacy of the Phase III trial after the submission of the protocol in April 2024 or at any time before the initiation of the study in September 2024.
In August of 2025, following the successful completion of the Phase III efficacy trial in which mRNA-1010 met all agreed-upon pre-specified primary endpoints, Moderna held a pre-submission meeting with CBER.
In its written feedback, CBER requested that supportive analyses on the comparator be included in the submission and indicated that the data would be a "significant issue during review of your BLA."
Moderna provided the additional analyses requested by CBER in its submission, including data from a separate Phase III trial (P303 Part C) comparing mRNA-1010 against a licensed high-dose influenza vaccine.
The company has said that at no time in the pre-submission written feedback or meeting did CBER indicate that it would refuse to review the file.
"This decision by CBER, 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," said Stéphane Bancel, CEO of Moderna.
"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 before starting."
"We look forward to engaging with CBER to understand the path forward as quickly as possible so that America's seniors and those with underlying conditions continue to have access to American-made innovations."
Moderna has said that it has requested a Type A meeting with CBER to understand the basis for the RTF letter.
The company has also posted the full letter on its website, citing that it wants to maintain transparency.