FDA Reverses Course, Agrees to Review Moderna's mRNA Flu Vaccine Application

The Food and Drug Administration agreed to review Moderna's experimental mRNA-based influenza vaccine after reversing an earlier decision to refuse the application. The agency accepted a modified regulatory approach following a meeting between Moderna and the FDA's Center for Biologics Evaluation and Research.

Following submission of the amended application, the FDA has accepted the biologics license application for review and assigned a Prescription Drug User Fee Act goal date of August 5, 2026. Pending review and FDA approval, mRNA-1010 would be available for US adults 50 years of age and older, including adults 65 and older, for the 2026/2027 flu season.

Under the new regulatory approach, Moderna is seeking full approval for the shot in adults ages 50 to 64 and an accelerated approval of the shot for people 65 and up. The latter means that upon approval, Moderna will have to conduct an additional post-marketing study in older adults to confirm its benefits.

The reversal came just a week after the FDA's surprise decision not to review the company's experimental flu vaccine application. The agency sent a refusal-to-file letter on Feb. 3 signed by the head of the Center for Biologics Evaluation and Research, calling the application inadequate for review. Such letters are rare, according to a 2021 study in JAMA Internal Medicine.

The FDA specifically took issue with Moderna's decision to compare its product to a standard, approved flu shot in a phase three trial, arguing that it "does not reflect the best-available standard of care" in the U.S. The agency repeatedly flagged that Moderna's clinical trial may inflate the benefit of its flu vaccine in adults 65 and older, the population most at risk of getting very sick from flu, by comparing it to a vaccine inferior to the standard of care.

According to the Centers for Disease Control and Prevention committee that sets U.S. vaccine policy, individuals 65 years old or older should receive one of the three following flu vaccines: Fluzone High-Dose, Flublok or Fluad. But Moderna compared its vaccine against a flu vaccine not on the committee's list, Fluarix. A closer inspection of the label of Fluarix shows that its efficacy drops off dramatically with age to just 14 percent efficacy from ages 50 to 64. The wide confidence interval for that 14 percent figure includes the possibility that the vaccine may not work at all in older individuals.

Moderna has disputed that reasoning, noting that FDA rules and guidance do not actually require trials to use the most advanced or highest-dose vaccine as a comparator in clinical studies. The company also said it was inconsistent with the FDA's prior written communication about the trial design, even before the study began, where the agency said using the standard flu shot would be "acceptable."

To test the safety and effectiveness of its mRNA flu shot, Moderna conducted two phase 3 trials. In one trial, more than 40,000 participants got the experimental shot or a standard flu shot. Another trial compared the mRNA vaccine to a standard shot and the high-dose shot recommended for seniors.

The company said it had a "constructive" meeting with the FDA and proposed a revised regulatory approach that addresses criticisms the agency made when refusing to accept the application last week, tailoring its new proposal to an older population. The chief executive officer stated that pending FDA approval, the company looks forward to making its flu vaccine available later this year so that America's seniors have access to a new option to protect themselves against flu.

Shares of the biotech company rose more than 6% on Wednesday. Moderna's stock value rose 6% from $43.93 at market close on 17 February to $46.70 at opening on 18 February. The company's market cap is $18.16bn.

Moderna said its new flu shot has been cleared for review in Australia, Canada and the European Union.

Using mRNA allows for quicker development of vaccines. During the COVID-19 pandemic, Moderna used the technology to develop one of the first vaccines available in the U.S. While traditional vaccines are based on a weakened virus, mRNA vaccines instead use a molecule called messenger RNA that the body recognizes as foreign. It prompts production of antibodies that allow the body to respond quickly if exposed to the virus itself.

Right now, how flu vaccines are made involves looking at what's going on the other side of the globe and predicting what strain will dominate in six months. That process takes time. The promise of mRNA technology is that you can do that with a little bit quicker turnaround, and you would be able to get a vaccine out much more quickly, especially in a flu pandemic scenario.

Influenza vaccines produced via mRNA technology will have a shorter production time than egg-based vaccines, cell-based vaccines, or recombinant vaccines. This decrease in production time means that the vaccines can be made closer to the start of flu season, thereby allowing for a better match to that season's circulating influenza strains.

The announcement clears a path forward for the vaccine, which is key to Moderna's experimental combination Covid-flu jab and the company's goal of breaking even by 2028.