^{A researcher works in the lab at the Moderna Inc. headquarters in Cambridge, Massachusetts, US, on Tuesday, March 26, 2024.}

^{Adam Glanzman | Bloomberg | Getty Image}

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Moderna disclosed that the U.S. Food and Drug Administration has refused to initiate a formal review of its application for mRNA-1010, the company’s investigational seasonal influenza vaccine. The decision represents a significant regulatory hurdle for the biotech firm and comes amid broader shifts in federal vaccine oversight policy.

Following the announcement, Moderna’s shares fell approximately 7 percent in after-hours trading, reflecting investor concern about delays in a product seen as central to the company’s long-term growth strategy beyond Covid-19 vaccines.

FDA Objects to Trial Design, Not Safety or Efficacy

According to Moderna, the FDA did not cite any specific safety signals or efficacy shortcomings in mRNA-1010. Instead, the agency declined to file the application based on concerns related to the clinical trial’s structure.

In a February 3 letter signed by Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research, the agency stated that Moderna’s pivotal Phase 3 trial did not meet its definition of an “adequate and well-controlled” study. The regulator objected to Moderna’s choice of comparator, arguing that using a standard approved flu vaccine did not reflect what it considers the “best-available standard of care.”

Moderna strongly disputes this interpretation. The company maintains that its trial design was discussed with and previously accepted by the agency before the Phase 3 program began. It also argues that existing FDA regulations and guidance do not require sponsors to use the highest-dose or most recently updated influenza vaccine as a comparator in clinical trials.

CEO Stéphane Bancel stated that declining to review a submission that uses an FDA-approved vaccine as a benchmark, and that followed a previously agreed-upon design, undermines efforts to advance innovative vaccine platforms.

The FDA has said it does not comment publicly on communications with individual companies.

Positive Phase 3 Results and Strategic Importance

mRNA-1010 completed Phase 3 trials last year, enrolling tens of thousands of adult participants across multiple countries. Moderna reported that the vaccine met all primary and secondary endpoints, demonstrating strong immune responses against the four influenza strains recommended for seasonal protection.

Seasonal influenza remains a significant public health burden. In the United States alone, the Centers for Disease Control and Prevention estimates that flu has resulted in between 9 million and 41 million illnesses annually over the past decade, with hospitalizations ranging from 140,000 to 710,000 and deaths between 12,000 and 52,000 per year. The global influenza vaccine market is valued at roughly $7 billion to $8 billion annually and is projected to grow steadily as vaccination coverage expands.

For Moderna, the flu shot is more than a standalone product. The company views mRNA-1010 as a foundational component of a broader respiratory vaccine portfolio that includes combination vaccines targeting both influenza and Covid-19. A successful flu platform would diversify revenue streams and reduce dependence on its Spikevax Covid vaccine, whose sales have declined sharply from pandemic-era peaks exceeding $18 billion annually.

Moderna has indicated that even with the FDA’s refusal to file the application at this stage, its 2026 financial guidance remains unchanged.

Broader Regulatory and Political Context

The development unfolds against the backdrop of evolving U.S. immunization policy. Over the past year, leadership changes and policy shifts within the Department of Health and Human Services and the FDA have signaled a more stringent approach to vaccine review and oversight.

Vinay Prasad, who returned to the FDA in August to lead CBER after previously departing the agency, has publicly advocated for tighter evidentiary standards for vaccines. He has emphasized rigorous trial design and clearer benefit-risk assessments, particularly in pediatric and broad population indications.

Industry analysts note that vaccine developers may face more detailed scrutiny of comparator choices, endpoint definitions, and statistical assumptions in future submissions. For biotechnology companies reliant on rapid regulatory pathways, such changes could extend development timelines and increase trial complexity and cost.

What Happens Next

Moderna has requested a meeting with the FDA to clarify expectations and determine a viable regulatory path forward. The company estimates that, depending on discussions and potential additional data requirements, the earliest possible approval for mRNA-1010 could now occur in late 2026 or 2027.

Beyond the United States, Moderna plans to seek regulatory approvals in Europe, Canada and Australia. Global diversification may help mitigate delays in any single market.

For investors and industry observers, the immediate issue centers on process rather than product safety. The FDA’s refusal to file does not constitute a rejection based on adverse findings; rather, it signals disagreement over whether the submitted evidence meets current regulatory standards.

Still, the episode underscores a broader reality for mRNA vaccine developers: as pandemic urgency fades, regulatory tolerance for expedited pathways has narrowed. Future growth in the vaccine sector will likely depend not only on scientific innovation but also on navigating a more exacting regulatory environment.