The FDA issued a refuse-to-file letter for Moderna’s mRNA influenza vaccine, asserting concerns about trial design and the choice of comparator, and declined to proceed with a formal review. Moderna said the decision was unexpected given prior communications, while company leaders have publicly described the letter as coming “out of the blue.” Agency officials including the vaccine review office have pointed to comparator choice and supporting analysis as unresolved issues. The action has rippled across the vaccine ecosystem: executives, investors and policy observers note growing regulatory uncertainty for respiratory vaccine programs and are recalibrating late-stage investments and development timelines accordingly.