FDA Issues Refusal-to-File Letter for Moderna’s mRNA-1010 Flu Vaccine

Moderna announced that the FDA’s Center for Biologics Evaluation and Research (CBER) has refused to initiate review of the biologics license application for its investigational influenza vaccine, mRNA-1010. The agency issued a Refusal-to-File (RTF) letter, preventing the submission from entering formal review despite Moderna having exercised a Priority Review Voucher.

The RTF letter cited a single deficiency: the comparator used in one Phase 3 study. CBER stated that the application did not include an “adequate and well-controlled” study with a comparator reflecting the “best-available standard of care.” Moderna noted that the agency did not identify any specific safety or efficacy concerns with mRNA-1010.

Moderna stated that CBER’s Refusal-to-File decision contrasts with prior regulatory feedback provided during an April 2024 Pre-Phase 3 consultation. After reviewing the Phase 3 protocol, CBER’s written guidance indicated that a licensed standard-dose influenza vaccine would be acceptable as a comparator. While the agency recommended vaccines preferentially advised for older adults, specifically Fluzone HD, Fluad, or Flublok for participants aged 65 years or older, it explicitly acknowledged Moderna’s plan to proceed with a standard-dose comparator in this age group provided appropriate informed consent language was included. Moderna noted that CBER did not raise objections or issue clinical hold comments following protocol submission or at any point prior to study initiation.

Following completion of the Phase 3 program, Moderna held a pre-submission meeting with CBER in August 2025. The agency requested supportive comparator analyses and indicated these would be a significant review issue. Moderna included the requested analyses in the BLA, including data from a separate Phase 3 trial comparing mRNA-1010 with a licensed high-dose influenza vaccine. Moderna stated that CBER did not signal a refusal to review at that time.

Stéphane Bancel, Chief Executive Officer of Moderna, expressed disappointment with the decision, highlighting that the RTF letter did not identify safety or efficacy deficiencies. Moderna has requested a Type A meeting with CBER to clarify the agency’s rationale and discuss a potential path forward.

The company also said the RTF letter is not expected to impact its 2026 financial guidance.

Outside the U.S., mRNA-1010 has been accepted for review in the European Union, Canada, and Australia. Moderna expects potential approvals could begin in late 2026 or early 2027, subject to ongoing regulatory evaluations.

Submission Overview

The BLA was supported by two Phase 3 studies enrolling 43,808 participants:

• P303 Part C: Safety and immunogenicity study in adults ≥65 years using a high-dose comparator
• P304: Safety and relative efficacy study in adults ≥50 years using a licensed standard-dose comparator

Moderna reported that both studies met pre-specified primary endpoints and demonstrated statistical superiority versus their comparators.

Reference

Moderna Receives Refusal-to-File Letter from the U.S. Food and Drug Administration for Its Investigational Seasonal Influenza Vaccine, mRNA-1010, 11 February 2026, News Release

Study of mRNA-1010 Seasonal Influenza Vaccine in Adults (IGNITE P303), ClinicalTrials.gov ID NCT05827978, https://clinicaltrials.gov/study/NCT05827978

Study of mRNA-1010 Compared with a Licensed Influenza Vaccine in Adults ≥50 Years of Age, ClinicalTrials.gov ID NCT06602024, https://clinicaltrials.gov/study/NCT06602024