FDA Won’t Review Moderna's mRNA Flu Vaccine Application

The FDA refused to accept Moderna's application to review its first mRNA seasonal flu vaccine. Another setback for the technology that's been a target of some Trump administration health officials.

The agency told Moderna its application didn't contain an "adequate and well-controlled" trial because the control arm didn't reflect the "best-available standard of care in the United States at the time of the study." According to a letter dated February 3 that Moderna posted online.

The FDA didn't identify any safety or efficacy concerns. They just said the trial design wasn't good enough.

Moderna said the refusal was inconsistent with previous feedback from the agency. They requested a meeting with FDA officials to understand how to proceed.

"The complete stunner here is at no point in any of this did anybody say that it was not adequate" to run its clinical trial the way it had discussed with the agency, Moderna's president Dr. Stephen Hoge told CNN Tuesday.

HHS Disagrees

Some HHS officials disagreed with that assessment. In a call Wednesday with reporters, spokesperson Andrew Nixon said, "The FDA rejected Moderna's application for filing because the company refused to follow very clear FDA guidance from 2024 to test its product in a clinical trial against a CDC-recommended flu vaccine to compare safety and efficacy."

It's rare for the FDA to issue a "refuse-to-file" letter. A 2021 study of almost 2,500 applications found only 4% received such letters.

What Moderna Did

Moderna used a standard-dose seasonal flu vaccine called Fluarix as a comparator in a 40,700-person clinical trial. The company said the FDA agreed with that plan in April 2024 but suggested it also include data comparing its vaccine with an approved high-dose flu vaccine for people over 65. Which the company said it did.

Moderna said as recently as August, in a meeting before submitting its application, the FDA suggested it would review the filing and assess issues with the comparator during that process.

But last week, the agency refused to do the review at all. The letter was signed by Dr. Vinay Prasad, director of the FDA's Center for Biologics Evaluation and Research, which oversees vaccine regulation.

Internal FDA Fight

Here's where it gets interesting. The decision not to accept Moderna's application came over the objection of some career staffers charged with reviewing the new flu vaccine according to two people familiar with the matter.

That included Dr. David Kaslow, who heads the FDA's vaccine office. He argued in favor of advancing the application. Kaslow declined to sign the agency's official refusal letter. That prompted Prasad to take the highly unusual step of putting his name on the decision.

So, the head of the vaccine office refused to sign the refusal letter. The director had to sign it instead. That's not very typical.

A senior FDA official speaking anonymously told reporters Wednesday there was a "healthy scientific debate" internally. But pointed out that during the previous administration, FDA staffers had "made a strong recommendation to use the appropriate flu shot as the control group in the over-65 population."

The Trump Administration Angle

Although the record-speed development of mRNA-based Covid vaccines during the pandemic was a chief accomplishment of Trump's first term, his second administration has withdrawn support for mRNA technology in infectious diseases.

HHS canceled 22 projects worth about $500 million focused on mRNA vaccine development in August. HHS Secretary Robert F. Kennedy Jr. claimed against evidence that "these vaccines fail to protect effectively against upper respiratory infections like COVID and flu."

The senior FDA official said Kennedy "was not directly or indirectly involved" with the decision to not accept Moderna's flu vaccine application. Said they have "been hopeful that mRNA technology would have some spinoff platform benefits outside of infectious diseases, but it just hasn't panned out yet."

Covid vaccines are estimated to have saved millions of lives. But apparently mRNA technology for infectious diseases hasn't "panned out."

What the Data Showed

Moderna's Phase 3 study showed results in June that the mRNA-based flu shot produced efficacy about 27% higher than Fluarix in adults 50 and older. A separate trial that assessed safety and immune response included comparison with a high-dose flu vaccine for people 65 and older and showed superiority, Moderna said.

So, the vaccine apparently worked better than the standard flu shot. But the FDA won't review it because they don't like how Moderna designed the trial. Even though the FDA apparently approved that trial design 18 months ago.

What Happens Next

Moderna had been waiting for the FDA review to start before moving its experimental combination flu and Covid mRNA vaccine into the FDA review process. That's now on hold as the company awaits a meeting and further guidance.

Meanwhile, the combination vaccine is moving forward in other countries.

"We do expect that our first approval will be … probably in Europe, and this year," Hoge said. "So that'll be a milestone event."

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