FDA rejects Moderna’s filing for mRNA-1010 flu vaccine

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Original story from Moderna (MA, USA).

Moderna, Inc. today announced the US Food and Drug Administration’s (FDA; MD, USA) Center for Biologics Evaluation and Research (CBER) has notified the Company that it will not initiate a review of the biologics license application (BLA) for its investigational influenza vaccine, mRNA-1010, and has issued a Refusal-to-File (RTF) letter. Moderna had exercised a Priority Review Voucher to facilitate a timely review of the application.

CBER’s RTF letter, signed by Center Director Vinayak Prasad, MD, MPH, identified the choice of a licensed standard-dose seasonal influenza vaccine comparator as the sole reason for the refusal to initiate the review of Moderna’s application. 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.” Neither the relevant regulation, 21 CFR § 314.126 (Adequate and well-controlled studies), nor the FDA’s guidance for industry on seasonal influenza vaccines contain 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.

The letter is inconsistent with previous written communications from CBER to Moderna. In April 2024, Moderna submitted the Phase 3 study protocol to CBER for review during a pre-Phase 3 consultation. 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 3 study, we recommend you use a vaccine preferentially recommended for use in older adults by the Advisory Committee on Immunization Practices (ACIP) (i.e., Fluzone HD, Fluad or Flublok) for participants >65 years of age in the study. Data on 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 3 trial after the submission of the protocol in April 2024 or at any time before the initiation of the study in September 2024.

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In August of 2025, following the successful completion of the Phase 3 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 3 trial (P303 Part C) comparing mRNA-1010 against a licensed high-dose influenza vaccine. 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, Chief Executive Officer 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 prior to 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 requested a Type A meeting with CBER to understand the basis for the RTF letter. In the interest of transparency, the Company has posted the full letter on its website, linked here.

mRNA-1010 has been accepted for review in the EU, Canada and Australia. Submissions in additional countries are planned for 2026. Moderna expects the earliest potential approvals for mRNA-1010 to begin in late 2026 or early 2027, subject to those ongoing regulatory reviews.

The Company does not expect an impact to its 2026 financial guidance based on the RTF from CBER.

About Moderna’s mRNA-1010 submission

Moderna’s mRNA-1010 BLA submission includes two positive Phase 3 studies that enrolled a total of 43,808 participants and met all pre-specified primary endpoints. Both Phase 3 designs were reviewed by FDA prior to study initiation. P303 Part C was a safety and immunogenicity study that compared mRNA-1010 against a high-dose comparator in adults aged 65 years or older. P304 was a safety and relative efficacy study that compared mRNA-1010 against a licensed standard-dose comparator in adults aged 50 years and older. In both Phase 3 studies, the primary endpoints showed statistical superiority of mRNA-1010 compared with the respective comparators. P303 has been published in a peer-reviewed publication and P304 has been submitted for publication.

The trial design for the P304 efficacy study, showing superiority over a licensed standard-dose influenza vaccine, is similar to that used to approve two licensed influenza vaccines that are preferentially recommended for adults aged 65 years or older in the US. Those approved products demonstrated a similar degree of statistically superior relative efficacy over a standard-dose influenza vaccine comparator as was achieved by mRNA-1010 in P304 [1][2]. One of these products used the same licensed standard-dose comparator (Fluarix®), which is licensed in the US for all adults, including for adults aged 65 years or older. Approximately 2 million US adults aged 65 years or older received a standard-dose influenza vaccine in the most recent influenza season [3][4].

Many countries outside the US do not preferentially recommend high-dose influenza vaccines over standard-dose influenza vaccines for adults aged 65 or older.[5]

This article has been republished from the following materials. Material may have been edited for length and house style. For further information, please contact the cited source. 

Source

  1. Sanofi Pasteur. Package Insert - Fluzone High-Dose Quadrivalent. US Food and Drug Administration, revised Jan 2019. Available from: www.fda.gov/media/132238/download [Accessed 16 Feb 2026].
  2. Fluzone High-Dose Quadrivalent Package Insert. US Food and Drug Administration. (2019), Available from: www.fda.gov/media/132238/download [Accessed 16 Feb 2026].
  3. Moderna analysis of commercially available pharmacy and medical claims data.
  4. Centers for Disease Control and Prevention. Influenza Vaccinations Administered in Pharmacies and Physician Medical Offices, Adults, United States. FluVaxView. (2025). Available from: www.cdc.gov/fluvaxview/dashboard/adult-vaccinations-administered.html [Accessed 16 Feb 2026].

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