FDA Blocks Review of Moderna's Groundbreaking mRNA Flu Vaccine in Shock Decision

A Refuse-to-File Letter That Stunned the Industry

The U.S. Food and Drug Administration has refused to even review Moderna's application for what would have been the world's first mRNA-based influenza vaccine, a decision the company says blindsided its leadership and contradicts guidance the agency itself provided before the pivotal trial began. The FDA issued a formal Refuse-to-File (RTF) letter targeting the biologics license application for mRNA-1010, Moderna's seasonal flu shot candidate, citing concerns not with the vaccine's safety or efficacy but with the design of the Phase 3 clinical trial.

The letter, dated February 3 and authored by top vaccine official Vinay Prasad, stated that the trial was not "adequate and well-controlled" because the comparator vaccine used in the study did not reflect the "best-available standard of care in the United States at the time of the study." Notably, the agency did not identify any specific safety or efficacy problems with mRNA-1010 itself.

The Comparator Controversy

At the heart of the dispute is which existing flu vaccine Moderna chose as the benchmark against which mRNA-1010 was measured. In its Phase 3 program, Moderna used a licensed standard-dose seasonal influenza vaccine as the comparator. The FDA now contends that Moderna should have used one of the enhanced vaccines preferentially recommended for adults over 65, such as Sanofi's Fluzone High-Dose, Seqirus's Fluad, or Sanofi's Flublok.

Moderna disputes that interpretation, pointing to a pre-Phase 3 consultation with the FDA's Center for Biologics Evaluation and Research (CBER) in April 2024, during which agency officials stated that a licensed standard-dose vaccine would be an acceptable comparator. CBER recommended, but did not require, the use of enhanced vaccines for the older-adult subgroup. Armed with that guidance, Moderna designed and executed its trial accordingly.

The company has requested a meeting with FDA officials to understand how to move forward and has described the refusal as inconsistent with prior agency feedback.

Strong Clinical Data Left on the Table

The rejected application contained data from two Phase 3 studies enrolling more than 43,800 participants. According to Moderna, both trials met all pre-specified primary endpoints and demonstrated statistical superiority of mRNA-1010 over their respective comparators, a result that, under normal circumstances, would position a vaccine candidate strongly for regulatory approval.

The Kennedy Factor

The FDA's decision lands in a political environment that has grown increasingly hostile toward vaccines and mRNA technology in particular. Health and Human Services Secretary Robert F. Kennedy Jr., a longtime anti-vaccine activist, oversees the agency and has already moved to dramatically slash childhood vaccine recommendations and cancel roughly $500 million in federal research funding earmarked for mRNA vaccine development.

Prasad, the FDA official who signed the RTF letter, was an outspoken critic of the government's pandemic response before being appointed to his current post under Kennedy's leadership. Critics argue that the refusal represents regulatory hostility dressed up as a procedural objection, a way to block mRNA technology without having to evaluate the underlying science on its merits.

International Regulators See It Differently

While the FDA has shut the door on review, regulatory agencies in other major markets have taken a different stance. Moderna has confirmed that mRNA-1010 has been accepted for regulatory review in the European Union, Canada, and Australia, with additional submissions planned throughout 2026. If those agencies approve the vaccine, it would create the unusual situation of an American-developed product being available to patients overseas but not in the United States.

What Comes Next

Moderna's stock took a hit on the announcement, and the broader mRNA sector felt the chill. The company's leadership must now decide whether to redesign its U.S. trial program with a different comparator, a process that could add years of delay, or to pursue alternative regulatory pathways. In the meantime, the decision raises uncomfortable questions about whether scientific rigor or political ideology is driving vaccine regulation in the United States during the Kennedy era.