FDA refuses to review Moderna’s application for mRNA flu vaccine, company says

The US Food and Drug Administration has refused to accept an application from Moderna to review its first mRNA seasonal flu vaccine, the company said Tuesday, in another setback for the technology that’s been a target of some Trump administration health officials.

The agency told Moderna that 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. It didn’t identify any safety or efficacy concerns, the company said.

Moderna said that the refusal was inconsistent with previous feedback from the agency and that it had 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 on Tuesday.

The US Department of Health and Human Services said “the FDA generally does not comment on regulatory communications to individual sponsors.”

Moderna used a standard-dose seasonal flu vaccine called Fluarix as a comparator in a 40,700-person clinical trial to demonstrate the experimental mRNA vaccine’s safety and efficacy. The company said the FDA had 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 added that as recently as August, in a meeting before it submitted its application for approval of the vaccine, the FDA suggested that it would review the filing and assess issues with the comparator during that process. The agency did note that there could be a “significant issue” with the data “during review” of the application, according to written feedback that Moderna shared.

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

Prasad was an outspoken critic of the government’s response to Covid-19 before he was appointed to the FDA under HHS Secretary Robert F. Kennedy Jr. He claimed late last year without providing details that Covid-19 vaccines resulted in deaths of 10 children and has said the agency will change its vaccine approval process.

Moderna is one of three manufacturers in the US of approved Covid-19 vaccines, along with Pfizer and Novavax. Moderna and Pfizer’s vaccines use mRNA technology. Pfizer also has mRNA-based flu vaccines in development.

Although the record-speed development of mRNA-based Covid-19 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, claiming against evidence that “these vaccines fail to protect effectively against upper respiratory infections like COVID and flu.”

Covid-19 vaccines are estimated to have saved millions of lives. The hope behind applying mRNA technology to seasonal flu vaccines is that it could improve how well they work, enable tailoring for geographic regions where different strains are circulating and lead to combinations with Covid-19 vaccines so people would need only one shot for protection against both viruses.

With currently approved technology, experts select flu strains for each fall’s seasonal vaccines during the preceding February. Hoge pointed out that mRNA vaccines can be manufactured much faster; for Covid-19 vaccines, he said, the design is decided in May or June, for shipping by August.

Choosing the strains closer to the start of flu season could potentially lead to a better match with circulating viruses, “and better matching equals, usually, better protection,” Hoge said.

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

Immune response is assessed in the laboratory by analyzing blood samples of people who’ve been vaccinated, while efficacy assessments typically involve seeing how well a vaccine protects against cases of the disease.

Moderna had been awaiting the start of the review of its flu shot before it moved its experimental combination flu and Covid-19 mRNA vaccine into the FDA review process, Hoge said. That’s now on hold as the company awaits a meeting and further guidance from the agency.

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.”