Moderna’s flu vaccine filing accepted for FDA review following regulatory about-face

The US FDA has belatedly accepted the Biologics License Application (BLA) for Moderna’s investigational seasonal influenza vaccine, mRNA-1010, for review. The company is seeking approval for the prevention of influenza in adults aged 50 years and older. This follows a procedural setback earlier this month, where the agency initially issued a Refusal-to-File letter regarding the application. Following a subsequent Type A meeting to resolve the agency’s feedback, the FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of August 5, 2026. If approved, mRNA-1010 would be the first mRNA-based seasonal influenza vaccine to enter the US market, marking a significant technological shift from the conventional egg-based and cell-based manufacturing platforms currently in use.

The BLA outlines a split regulatory pathway based on patient age. Moderna is pursuing full approval for adults aged 50 to 64 years and accelerated approval for adults aged 65 years and older. The accelerated approval pathway typically allows for earlier clearance of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint, such as immunogenicity, pending verification of clinical benefit in post-marketing trials. Accordingly, the filing includes a post-marketing requirement for Moderna to conduct a confirmatory study in the older adult population. While full prescribing information is not yet public, the vaccine is administered as a single intramuscular injection, consistent with standard seasonal influenza immunization schedules.

The FDA’s initial refusal to file the BLA centered on a disagreement regarding the clinical trial’s control arm for older participants. In the pivotal P304 trial, Moderna compared mRNA-1010 to a licensed standard-dose influenza vaccine. However, for adults aged 65 and older, the US CDC preferentially recommends “enhanced” vaccines—such as high-dose or adjuvanted options—to compensate for age-related immune decline. CBER Director Dr. Vinayak Prasad asserted that the use of a standard-dose comparator for this specific demographic failed to reflect the “best-available standard of care,” rendering the study’s design inadequate for a standard review. Moderna contested this, noting that the agency had previously categorized a standard-dose comparator as “acceptable” in 2024 and that existing federal regulations do not explicitly mandate “best-available” controls for approval. The split regulatory pathway for mRNA-1010 appears to be the solution to that impasse, balancing standard evidence requirements with the accelerated needs of the senior population.

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Clinical trial evidence

The submission is supported by data from pivotal Phase III clinical trials, including the P303 (immunogenicity) and P304 (efficacy) studies. The P304 trial (NCT06602024), a randomized, observer-blind, active-controlled study, evaluated the efficacy of mRNA-1010 compared to a licensed standard-dose inactivated influenza vaccine in adults aged 50 years and older. Results demonstrated that mRNA-1010 achieved a 26.6% higher relative vaccine efficacy against laboratory-confirmed influenza compared to the standard-dose comparator. Additionally, the P303 study (NCT05827978) assessed immunogenicity, showing that the vaccine elicited superior immune responses against influenza A/H1N1, A/H3N2, and influenza B/Victoria strains compared to a standard-dose comparator.

Scientific and market context

Seasonal influenza remains a significant public health burden, with vaccine effectiveness often limited by the long lead times required for egg-based manufacturing, which can result in mismatches between the vaccine strain and circulating viruses. The mRNA platform used for mRNA-1010 targets the hemagglutinin (HA) protein of the influenza virus and offers the potential for shorter development timelines and more precise strain matching. Currently, the standard of care for adults aged 65 and older includes enhanced vaccines—such as high-dose or adjuvanted formulations—which are preferentially recommended by the CDC’s Advisory Committee on Immunization Practices (ACIP) over standard-dose options due to the effects of immunosenescence in this population. The FDA’s initial hesitation regarding Moderna’s filing reportedly centered on the use of a standard-dose comparator rather than these enhanced vaccines for the older demographic.

Moderna’s mRNA-1010 joins a competitive pipeline of next-generation influenza vaccines but currently leads in regulatory status. Pfizer is also developing an mRNA-based influenza vaccine; however, its Phase III data released in late 2025 showed mixed results, meeting efficacy endpoints for influenza A strains but missing non-inferiority targets for influenza B strains. Meanwhile, GSK continues to advance its own mRNA influenza candidate, which is currently in Phase II development. In contrast, Sanofi recently announced the deprioritization of its standalone mRNA seasonal flu program, opting instead to focus on its proprietary high-dose and recombinant protein flu franchises alongside mRNA development for pandemic influenza.