The Food and Drug Administration (FDA) has refused to review Moderna’s application for its mRNA-based influenza vaccine, mRNA-1010, the company announced Wednesday. The rejection does not stem from safety or efficacy concerns, but rather from questions regarding the study design used to evaluate the vaccine.
In a letter to Moderna, Dr. Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research (CBER), stated that the application lacked an “adequate and well-controlled” study, citing the comparator used for evaluation as the primary issue. The study compared mRNA-1010 to the standard-dose seasonal influenza vaccine currently approved by the FDA.
Moderna disputes this assessment, stating that the FDA’s decision contradicts previous communications. According to a press release, CBER indicated in 2024, when reviewing Moderna’s phase 3 study protocol, that using a licensed standard-dose influenza vaccine as a comparator would be “acceptable.” The agency even suggested prioritizing vaccines “preferentially recommended” by the CDC’s Advisory Committee on Immunization Practices for older adults, while still allowing the use of a standard dose vaccine with informed consent.
Further, Moderna claims that upon completion of the phase 3 trial in 2025, CBER requested supportive analyses on the comparator, which were subsequently provided. At no point, Moderna asserts, did the agency suggest the application would be rejected based on the comparator selection.
“The arbitrary and unpredictable nature of the FDA’s decision — after Moderna had already consulted with them regarding the trial’s characteristics — is of major concern,” said Dr. Amesh Adalja, senior scholar at the Johns Hopkins Center for Health Security. “Companies need predictability if they are going to invest a billion dollars to develop a new product. If the regulatory pathway is subject to arbitrary changes, they will no longer be willing to make such investments.”
Phase 3 trial data released last year showed mRNA-1010 had a relative efficacy of 26.6% (95% CI, 16.7%-35.4%) compared to the licensed vaccine across all study participants, with even higher efficacy observed in participants aged 65 years or older. The vaccine’s safety profile was also reported as similar to previous trials, with injection site pain being the most common local reaction and fatigue, headache and myalgia as the most common systemic reactions.
The FDA’s decision arrives amid a shifting landscape for mRNA vaccines in the United States. Recent changes in leadership at the Department of Health and Human Services (HHS) and the Advisory Committee on Immunization Practices (ACIP) have included public criticism of COVID-19 mRNA vaccines and related policies. In August, HHS canceled approximately $500 million in funding for mRNA vaccine development, a move described by experts as potentially damaging to scientific advancement.
Despite these developments, research into mRNA technology continues beyond COVID-19, with applications being explored for influenza, respiratory syncytial virus (RSV), cancer, cystic fibrosis, and rare pediatric conditions. Adalja noted that expanding the mRNA vaccine platform to include influenza could be beneficial, “given the speed with which updates and strain changes can be made,” potentially reducing the lead time required for vaccine development and allowing for later strain inclusion decisions.
Moderna has requested a meeting with CBER to discuss the basis for the refusal-to-file letter.
