The FDA has approved Moderna’s mRNA seasonal influenza vaccine, mFlusiva, for use in adults aged 50 years and older. This action marks the first influenza vaccine built on mRNA technology to reach the US market. The approval represents a significant step for the company’s platform beyond COVID-19.
The indication’s approval was based on efficacy data from the phase 3 FLUENT trial.
This study was a randomized, observer-blind, active-controlled, case-driven research effort.
It randomly assigned adults 50 years of age or older to receive either the trivalent mRNA vaccine or a licensed standard-dose comparator.
The mRNA vaccine contained a dose of 37.5 μg, which includes 12.5 μg of each strain.
The primary efficacy end point was relative vaccine efficacy against reverse-transcriptase–polymerase chain reaction (RT-PCR)–confirmed, protocol-defined influenza-like illness caused either by influenza A or B.
A total of 40,703 adults were enrolled in the trial.
About half of the participants received the mRNA vaccine, and the remainder received a licensed standard-dose comparator vaccine.
According to data published in the New England Journal of Medicine, mFlusiva met all primary end points.
The trial demonstrated approximately 26.6% relative efficacy against protocol-defined influenza-like illness caused by influenza A or B.
Solicited adverse events were more common with the mRNA vaccine than with standard-dose comparators.
Injection-site pain occurred in 65.8% of patients, fatigue in 45.1%, and headache in 37.8%.
However, the FLUENT investigators reported that most adverse events were considered mild to moderate and transient.
Regulatory Hurdles Prior to Authorization
The path to approval was not straightforward.
In February 2026, the FDA’s Center for Biologics Evaluation and Research issued a refusal-to-file letter for the original mFlusiva application.
The agency declined to review the application at all.
The letter, signed by then-CBER director Vinay Prasad, MD, MPH, stated the sole reason for the refusal was Moderna’s use of a licensed standard-dose influenza vaccine as the comparator in its trial.
The agency argued this did not represent the “best-available standard of care” for older adults.
Neither federal regulation nor FDA guidance explicitly required such a comparator.
The agency did not raise concerns regarding the vaccine’s safety or efficacy.
About one week after the refusal-to-file letter, following public disclosure of the decision and Moderna’s objections, the FDA reversed its stance.
The company proposed a revised, age-stratified regulatory strategy.
This plan involved full approval for adults aged 50 to 64 years and accelerated approval for adults 65 years and older alongside a postmarketing study using a high-dose comparator in the older cohort.
The agency accepted the amended application with a Prescription Drug User Fee Act date of August 5, 2026.
In June 2026, the FDA’s Vaccines and Related Biological Products Advisory Committee unanimously voted to recommend mFlusiva for adults aged 50 years and older.
This was the panel’s first review of a new vaccine application since May 2023.
They accepted it.
