Moderna receives refusal to file letter for its investigational influenza vaccine, mRNA-1010

Moderna has recently announced that the U.S. FDA Center for Biologics Evaluation and Research has notified the Company that it will not initiate a review of the biologics license application for its investigational influenza vaccine, mRNA-1010, and has issued a Refusal-to-File letter.

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.”

Note that 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 ACIP 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.”

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.”

“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.”

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Related Topics and Keywords

Moderna, mRNA-1010, vaccine