FDA Refuses to Review Moderna's mRNA Flu Vaccine
The U.S. Food and Drug Administration has refused to review Moderna's mRNA-based influenza vaccine. This regulatory setback highlights the persistent risks associated with developing and gaining approval for innovative advanced therapies, even for established players in the mRNA space.
- The specific vaccine candidate is mRNA-1010, and the FDA's Refusal-to-File (RTF) letter was signed by Dr. Vinayak Prasad, director of the Center for Biologics Evaluation and Research (CBER). The refusal was not based on any identified safety or efficacy concerns but on the trial's design. - The core issue cited by the FDA was that the Phase 3 clinical trial used a standard-dose licensed influenza vaccine as its comparator, which CBER argued did not reflect the "best-available standard of care" for adults over 65. - Moderna has disputed this, stating the decision contradicts prior FDA guidance from April 2024, which had deemed a standard-dose comparator acceptable for the study design. The company's Biologics License Application included data from two Phase 3 studies with more than 43,800 participants. - The pivotal P304 study showed mRNA-1010 had a 26.6% higher relative vaccine efficacy than the standard-dose comparator in adults aged 50 and older. Efficacy was also demonstrated against individual strains, including 29.6% for A/H1N1. - While the review is halted in the U.S., regulatory bodies in the European Union, Canada, and Australia have accepted the application for mRNA-1010 and are proceeding with their reviews. - This setback also affects Moderna's combination flu and COVID-19 vaccine candidate, mRNA-1083, which uses mRNA-1010 as its influenza component. The U.S. regulatory path for this combination vaccine is now uncertain. - Competitors are also in the mRNA flu vaccine space; Pfizer has a candidate in Phase 3 trials. However, Sanofi recently discontinued its program for a seasonal mRNA flu vaccine, citing struggles against influenza B strains, to focus on its existing high-dose and recombinant protein vaccines. - The manufacturing of mRNA vaccines presents unique challenges compared to traditional egg-based methods, including the need for a cost-effective, scalable in-vitro transcription and purification platform, as well as maintaining stability through cold-chain logistics.
