Moderna gave notice that the US FDA’s Center for Biologics Evaluation and Research (CBER) issued a refusal-to-file letter for its investigational seasonal influenza vaccine mRNA-1010. The vaccine’s market approval process was halted prior to the CBER’s initiation of a review process.

The FDA determined that the submission did not meet filing requirements because the supporting clinical data were “inadequate and not well-controlled”, particularly in how the vaccine was compared with the standard of care in the trial design, the company said in its filing. No safety or efficacy concerns were raised with the vaccine itself.

mRNA-1010 had been developed as a seasonal influenza vaccine using Moderna’s mRNA platform, which the company has positioned as a flexible alternative to traditional flu shots. Moderna previously expected to complete global regulatory submissions for mRNA-1010, including in the US, Canada, Europe, and Australia by early 2026.

In response to the FDA action, Moderna notes that the RTF was issued despite the company previously confirming Phase III design for mRNA-1010 with the US FDA in a pre-trial meeting, and in writing from the CBER. The firm had exercised a priority review voucher to accelerate the course of its BLA. Moderna will now seek an urgent meeting with the agency to discuss next steps and clarify data expectations for a future filing. The company noted that regulatory reviews are ongoing in markets outside the United States, with submissions accepted or planned in Canada, Europe, and Australia.

Implications

Companies involved in mRNA technology are transitioning from the emergency development of COVID-19 vaccines (and accompanying accelerated regulatory handling) to traditional, highly specific requirements for trial design and comparative data.In addition, the mRNA field has expanded significantly beyond COVID-19 into oncology (personalized cancer vaccines), rare genetic disorders, and complex respiratory infections like RSV and Influenza.

Prior to today’s announcement, Moderna’s mRNA‑1010 was the most advanced stand‑alone seasonal flu mRNA program, with multiple completed Phase III studies. Other companies potentially impacted by the news include Pfizer/BioNTech, who are advancing stand‑alone seasonal influenza modRNA (modified RNA) candidates and a COVID–flu combination program into Phase III, but have publicly disclosed mixed outcomes for the combo immunogenicity objectives. Seqirus (CSL) is clinically testing a self-amplifying mRNA (sa‑mRNA) influenza approach in Phase I. Sanofi initiated mRNA seasonal flu work with Translate Bio (e.g., MRT‑5400/5401) but later publicly indicated deprioritization of seasonal mRNA flu (while still pursuing pandemic flu mRNA). GSK/CureVac have reported Phase II headline data for a seasonal influenza mRNA program and indicate preparation for Phase III (per company communications).