FDA Reverses Course, Agrees to Review Moderna’s mRNA Flu Vaccine

The FDA’s decision to reverse its "Refusal to File" (RTF) for Moderna’s seasonal influenza vaccine, mRNA-1010, marks a significant and rare regulatory pivot. Typically, an RTF is a major setback for a pharmaceutical company, signaling that an application is fundamentally incomplete or has significant deficiencies that prevent a substantive review. For the FDA to rescind such a decision within a short period suggests that Moderna was able to rapidly address the agency’s concerns—likely related to administrative data or specific assay validations—rather than deep-seated clinical failures. This reversal is a major victory for Moderna, which is under intense pressure to diversify its revenue stream as sales of its COVID-19 vaccine, Spikevax, continue to decline from pandemic peaks.

The vaccine candidate at the center of this review, mRNA-1010, is a quadrivalent vaccine targeting the four influenza strains recommended by the World Health Organization: A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. In clinical trials, mRNA-1010 has demonstrated strong immunogenicity, particularly against Influenza A strains, which are responsible for the majority of flu-related hospitalizations and deaths. While earlier data showed some challenges in achieving non-inferiority against Influenza B strains compared to existing vaccines, Moderna’s subsequent Phase 3 trials and updated formulations appear to have satisfied the regulatory threshold for a formal review. The move to mRNA technology for flu vaccines is seen as a potential game-changer for the industry, offering the ability to manufacture doses much faster than traditional egg-based methods, which require a six-month lead time and are susceptible to "egg-adaptation" mutations that can reduce vaccine efficacy.

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The FDA’s decision to reverse its "Refusal to File" (RTF) for Moderna’s seasonal influenza vaccine, mRNA-1010, marks a significant and rare regulatory pivot.

Strategically, the FDA’s acceptance of the application puts Moderna in a head-to-head race with other pharmaceutical giants. Sanofi, GSK, and CSL Seqirus currently dominate the multi-billion dollar global influenza market. Pfizer is also developing its own mRNA-based flu vaccine, but Moderna’s progress toward a potential 2026-2027 season launch could give it a crucial first-mover advantage in the mRNA flu space. Furthermore, mRNA-1010 serves as the foundational component for Moderna’s broader respiratory strategy, which includes a combination vaccine targeting COVID-19, flu, and potentially RSV in a single shot. Success with the standalone flu vaccine is a necessary precursor to the approval of these highly anticipated combination products, which Moderna believes will simplify seasonal immunization and improve compliance.

Looking ahead, the biotech industry will be watching for the FDA’s assignment of a PDUFA (Prescription Drug User Fee Act) date, which will establish the deadline for a final approval decision. Given the public health importance of influenza and the novel nature of the mRNA platform for this indication, the FDA may convene an Advisory Committee (AdCom) meeting to publicly debate the clinical data and safety profile of mRNA-1010. Investors and healthcare providers will be particularly focused on the vaccine’s reactogenicity—the common side effects like fever or arm pain—which have historically been higher for mRNA vaccines than for traditional flu shots. If Moderna can prove that the superior efficacy and manufacturing speed of mRNA-1010 outweigh its side-effect profile, it could fundamentally reshape the seasonal vaccine landscape.