The U.S. Food and Drug Administration has declined to review Moderna’s application for its first mRNA seasonal flu vaccine, a surprising decision that could delay innovative vaccine development and has prompted Moderna to seek clarification from regulators.
In a refusal-to-file letter dated February 3, the FDA stated that Moderna’s clinical trials were not adequate because they compared the new mRNA vaccine, mRNA-1010, to a standard-dose flu shot, Fluarix, rather than the best-available standard of care, which includes high-dose vaccines for older adults. Moderna countered that it had followed FDA guidance, including comparisons with high-dose vaccines in adults over 65, and that the agency had previously agreed to review the application. Dr. Stephen Hoge, Moderna’s president, expressed shock, noting no safety or efficacy concerns were identified and that the refusal was inconsistent with earlier feedback.
The decision is rare, with only about 4% of applications receiving such letters, and it was signed by Dr. Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research. Prasad, appointed under the Trump administration, has been critical of COVID-19 vaccines and has indicated plans to revise vaccine approval processes. This move aligns with broader shifts in the administration’s stance on mRNA technology, including funding cuts for related projects announced last year.
Moderna’s phase 3 trials showed that mRNA-1010 had efficacy about 27% higher than Fluarix in adults 50 and older, and it elicited superior immune responses compared to high-dose vaccines in those over 65. The mRNA technology allows for faster manufacturing and potential better matching to circulating flu strains, which could improve protection. However, the refusal delays not only this flu vaccine but also Moderna’s planned combination flu and COVID-19 mRNA vaccine, which is now on hold in the U.S.
Experts warn that this decision could discourage investment in new vaccines and create regulatory uncertainty. Dorit Reiss, a law professor at UC Law San Francisco, called it arbitrary and problematic, suggesting it might hinder future influenza vaccine development. Meanwhile, Moderna’s application is under review in other regions, including the European Union, Canada, and Australia, with approvals expected there first, potentially as early as this year.
The refusal highlights ongoing tensions between vaccine developers and regulatory bodies under the current administration, which has withdrawn support for mRNA technology in infectious diseases. This could have long-term implications for public health, especially in preparing for future pandemics where rapid vaccine updates are crucial. Moderna remains hopeful for a resolution after meeting with FDA officials, but the setback underscores the challenges in advancing innovative vaccine technologies amidst political changes.
