Moderna secures historic FDA approval for mRNA flu shot mFlusiva

USA—Moderna has secured U.S. approval for mFlusiva, its mRNA-based influenza vaccine, overcoming a regulatory setback earlier this year and paving the way for the first mRNA flu shot to reach the U.S. market.

The FDA approved mFlusiva late Wednesday to prevent seasonal influenza in adults aged 50 years and older.

The decision gives Moderna its fourth FDA-approved product and expands the company’s mRNA vaccine portfolio beyond COVID-19 and respiratory syncytial virus (RSV).

The vaccine’s path to approval became uncertain in February, when the FDA issued Moderna a rare refusal-to-file (RTF) letter over concerns about the design of a phase 3 trial for the vaccine, then known as mRNA-1010.

Moderna publicly challenged the decision, and the FDA reversed course slightly more than a week later, agreeing to review the company’s application.

FDA raises concerns over trial comparator

The agency’s initial concerns centered on the comparator used in one of the clinical trials supporting mFlusiva’s application.

Moderna had compared its vaccine with a standard-dose influenza vaccine, while the FDA argued that the study should have used the “best-available standard of care.”

Moderna disagreed with the assessment, noting that the FDA had not previously raised the comparator as an issue during discussions about the trial’s design.

The vaccine subsequently cleared another regulatory hurdle when the FDA’s Vaccines and Related Biological Products Advisory Committee unanimously determined that mFlusiva’s benefits outweighed its risks in adults aged 50 to 64 and those aged 65 and older.

Approval supported by two phase 3 trials

The FDA granted traditional approval for mFlusiva in adults aged 50 to 64 and accelerated approval for those aged 65 and older.

The decision was supported by data from two phase 3 trials.

In adults aged 50 to 64, researchers assessed mFlusiva’s relative vaccine efficacy, among other measures, against a standard-dose influenza vaccine.

In the study involving adults aged 65 and older, researchers compared mFlusiva with a high-dose inactivated influenza vaccine, with immunogenicity serving as the primary objective.

Because the FDA granted accelerated approval for the older population, Moderna must conduct a postmarketing trial to confirm the vaccine’s clinical benefit in this group.

Moderna targets 2026-2027 flu season

Moderna expects to make mFlusiva available in the U.S. ahead of the 2026-2027 respiratory virus season.

The vaccine will join the company’s existing respiratory vaccine portfolio, including Spikevax and mNexspike for COVID-19 and mResvia for RSV.

“Flu remains a significant public health challenge, and mFlusiva provides an important new option for America’s seniors,” Moderna CEO Stéphane Bancel said in a statement.

Outside the U.S., Moderna has submitted mFlusiva for regulatory review in the European Union, Canada and Australia.

Meanwhile, in Europe, the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of Moderna’s mCombriax for adults aged 50 and older.

The mRNA-based combination vaccine is designed to provide protection against both COVID-19 and influenza in a single shot.