The FDA declined to review Moderna’s mRNA flu vaccine application for its mRNA-1010 product, and based its decision on it choice of comparator in a phase 3 trial, despite the absence of safety or efficacy concerns and prior FDA agreement on the study design. Moderna requested a meeting to understand the path forward with the vaccine.
The FDA has declined to initiate a review of Moderna’s biologics license application (BLA) for its investigational influenza vaccine, mRNA-1010, issuing a Refusal-to-File (RTF) letter that hinges on trial design rather than concerns about the vaccine’s safety or effectiveness.
Moderna announced that the FDA’s Center for Biologics Evaluation and Research (CBER) determined it could not review the application because the company used a licensed standard-dose seasonal influenza vaccine as the comparator in a pivotal phase 3 efficacy study. According to the RTF letter, signed by CBER Director Vinayak Prasad, MD, MPH, the comparator did not reflect the “best-available standard of care,” and therefore did not meet the requirement for an “adequate and well-controlled” study.
Moderna disputes this interpretation, noting that neither FDA regulations governing adequate and well-controlled trials nor FDA guidance on seasonal influenza vaccines explicitly require a comparator reflecting the “best-available standard of care.” The RTF letter also did not identify any deficiencies related to the safety, immunogenicity, or efficacy of mRNA-1010.
The company emphasized that the decision appears inconsistent with prior written communications from CBER. During an April 2024 pre-phase 3 consultation, CBER stated that using a licensed standard-dose influenza vaccine as a comparator would be acceptable, while recommending—but not requiring—the use of vaccines preferentially recommended for adults older than 65 years, such as Fluzone HD, Fluad, or Flublok. CBER did not place the trial on clinical hold or raise objections to the study design before enrollment began in September 2024.
Following successful completion of the phase 3 program, Moderna met with CBER in August 2025 ahead of submitting the BLA. While CBER flagged the comparator analysis as a “significant issue during review,” it did not indicate that the application would be refused. Moderna provided additional analyses as requested, including data from a separate phase 3 trial comparing mRNA-1010 with a licensed high-dose influenza vaccine in adults aged 65 years or older.
The FDA’s refusal centers on trial comparator selection, not on safety, immunogenicity, or efficacy issues with mRNA-1010.
Moderna argues the decision contradicts earlier FDA guidance and established regulatory precedent for influenza vaccine approvals.
While US review is paused, mRNA-1010 continues to advance through regulatory reviews in multiple international markets.
“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,” Moderna CEO Stéphane Bancel, said in a statement. He added that Moderna looks forward to engaging with CBER “to understand the path forward as quickly as possible.”
The BLA submission included data from 2 phase 3 studies enrolling more than 43,800 participants. Both trials met all pre-specified primary endpoints and demonstrated statistical superiority of mRNA-1010 versus their respective comparators. Moderna also noted that the P304 trial design mirrors those used to approve existing influenza vaccines now preferentially recommended for older adults in the US.
While the US review is on hold, mRNA-1010 has been accepted for regulatory review in the European Union, Canada, and Australia, with additional submissions planned for 2026. Moderna expects potential approvals outside the US to begin in late 2026 or early 2027 and does not anticipate an impact on its 2026 financial guidance.
