FDA scientists raised significant questions about the evidence supporting Moderna's mRNA-based influenza vaccine mFlusiva ahead of a crucial advisory committee vote.

The agency flagged evidence gaps in key patient populations that have potential to complicate its path to approval even as the agency found no major deficiencies in the data. The concerns were detailed in a briefing document filed ahead of a June 18 meeting of the Vaccines and Related Biological Products Advisory Committee, which will vote on whether the benefits of mFlusiva outweigh its risks in adults aged 50 to 64 and in those 65 and older.³

FDA is expected to make a final decision on the application by August 5.¹

What did FDA reviewers find?

FDA staff scientists concluded that mFlusiva met prespecified success criteria in its Phase III pivotal trial, but raised four issues they want the advisory panel to weigh carefully.¹ In Study P304, which enrolled 40,805 adults across 301 sites in 11 countries, mFlusiva demonstrated a relative vaccine efficacy of 26.6% against RT-PCR-confirmed influenza-like illness compared with a standard-dose comparator vaccine (95% CI: 16.7–35.4).1,2 When measured against higher-level healthcare outcomes such as emergency room visits, hospitalizations, and urgent care use, efficacy rose to 47.9%.¹

Despite those findings, reviewers identified several limitations that "lower the applicability of the efficacy data to a substantial portion of the intended patient population.”² The trial drew on a single flu season of data, leaving open how the vaccine would perform against different circulating strains in future years.

The confidence interval for mFlusiva's efficacy against influenza B/Victoria crossed zero due to low case accrual for that strain, leaving its protective effect against influenza B uncertain.¹ The vaccine was not studied in immunocompromised patients or very frail older adults, two groups at the highest absolute risk of severe flu-related complications and those most likely to respond differently to mRNA-based vaccine platforms.^1,2 Currently, no data exists on co-administration with other routinely recommended respiratory vaccines, including Covid-19, RSV, and pneumococcal vaccines.

How is Moderna seeking approval?

Moderna is pursuing a bifurcated regulatory strategy. For adults between 50 and 64, it is seeking traditional approval based on the clinical efficacy data from Study P304, while for adults 65 and older, a group for which FDA notes that high-dose, recombinant, or adjuvanted influenza vaccines are preferentially recommended by the CDC, Moderna is seeking accelerated approval based on immunogenicity data from a separate trial, Study P303 Part C.¹

In that study of 3,003 participants aged 65 and older, mFlusiva met prespecified noninferiority and superiority criteria against Fluzone High-Dose on antibody geometric mean titers and seroconversion rates at Day 29 across all four vaccine-matched influenza strains, with immune responses remaining higher at the six-month follow-up endpoint.¹ As a condition of accelerated approval, Moderna has agreed to conduct a Phase IV confirmatory trial to establish clinical benefit in that age group.

The advisory committee meeting caps an unusually turbulent regulatory journey for mFlusiva, as Moderna previously withdrew a related application for a combination Covid and flu vaccine in 2025 after FDA requested more data from its flu-preventing component. When Moderna later assembled those data and resubmitted a standalone influenza application, it received a refuse-to-file letter issued by then-acting CBER director Vinay Prasad, who alleged the company's key trial used an inadequate comparator.

Moderna argued it had been blindsided by the decision and that it contradicted prior agency guidance. FDA then reversed course days later amid public backlash, accepting the application for review, a reversal that drew significant attention given the agency's broader leadership turmoil at the time.

Both Prasad and former commissioner Marty Makary have since departed FDA as part of a White House-directed overhaul, meaning the final approval decision will rest with different leadership than that which initially refused to review the application.

Sources

1. FDA Briefing Document BLA# 125869/0 Influenza Vaccine, mRNA (Proposed Trade Name: mFlusiva) Applicant: Moderna TX, Inc. FDA June 16, 2026 https://www.fda.gov/media/193130/download
2. FDA staff scrutinizes evidence supporting Moderna’s flu vaccine BioPharmaDive June 16, 2026 https://www.yahoo.com/news/science/articles/fda-staff-scrutinizes-evidence-supporting-115900036.html?guccounter=1&guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&guce_referrer_sig=AQAAAGL4IO2QD5GBfXSk48MWTERNenfGe-gH2ZOAOs4ZdJu8RV-G9GSLFqyzcuzOZvHjQgTxi6VEsr55YM9pwFr-7xMZrXjodRwW83ANbC8QXQhLiuGSfw6awaDkLt34LrIfXh_GhFqW7UN_RyB71OLPvvvj0VsQwUfMl_3ZkAzMlCP3
3. Vaccines and Related Biological Products Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments-Safety and Effectiveness of MFLUSIVA (Influenza Vaccine, mRNA) Manufactured by Moderna TX Inc. Federal Register May 22, 2026 https://www.federalregister.gov/documents/2026/05/22/2026-10321/vaccines-and-related-biological-products-advisory-committee-notice-of-meeting-establishment-of-a