The U.S. Food and Drug Administration has declined to accept a request from Moderna to review its first mRNA seasonal flu vaccine, the company said Tuesday, in another setback for the technology that has been the target of Trump administration health officials.
The agency told Moderna that its application did not contain an “adequate and well-controlled” study because the control arm did not reflect “the best standard of care available in the United States at the time of the study,” according to a Feb. 3 letter that Moderna posted online. It has not identified any safety or efficacy issues, the company said.
Moderna said the refusal was at odds with previous feedback from the agency and that it had requested a meeting with FDA officials to figure out how to proceed.
“The complete shocker here is at no point did anyone say it was inappropriate” to conduct its clinical trial as it had discussed with the agency, Moderna President Dr. Stephen Hoge told CNN on Tuesday.
The US Department of Health and Human Services stated that “FDA generally does not comment on regulatory communications to individual sponsors.” It is rare for the FDA to issue a “refusal to file” letter; a 2021 study of nearly 2,500 claims submitted to the agency found that only 4 percent received such letters.
Moderna used a standard-dose seasonal flu vaccine called Fluarix as a comparator in a 40,700-person clinical trial to demonstrate the safety and effectiveness of the experimental mRNA vaccine. The company said the FDA agreed to that plan in April 2024, but suggested it also include data comparing its vaccine to a high-dose flu vaccine approved for people over 65, which the company said it did.
Moderna added that in August, in a meeting before submitting its application for approval of the vaccine, the FDA suggested it would review the submission and assess problems with the comparator during the process. The agency noted that there could be a “significant issue” with the data “during review” of the app, 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 being appointed to the FDA under HHS Secretary Robert F. Kennedy Jr. He claimed late last year, without providing details, that Covid-19 vaccines had led to the deaths of 10 children and said the agency would change its vaccine approval process.
Moderna is one of three US manufacturers of approved Covid-19 vaccines, along with Pfizer and Novavax. Moderna and Pfizer vaccines use mRNA technology. Pfizer also has mRNA-based flu vaccines in development.
Although the record-breaking development of mRNA-based Covid-19 vaccines during the pandemic was a key achievement 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, saying “these vaccines fail to effectively protect against upper respiratory infections such as COVID and influenza.”
It is estimated that Covid-19 vaccines have saved millions of lives. The hope behind applying mRNA technology to seasonal flu vaccines is that it could improve how well they work, allow adaptation for geographic regions where different strains circulate, and lead to combinations with Covid-19 vaccines so that people only need one shot for protection against both viruses.
With currently approved technology, experts select flu strains for each fall’s seasonal vaccines in the previous February. Hoge pointed out that mRNA vaccines can be manufactured much more quickly; for Covid-19 vaccines, he said, the design is decided in May or June, for delivery by August.
Selecting strains closer to the start of the flu season could lead to a better match with circulating viruses, “and a better match usually means better protection,” Hoge said.
Moderna’s Phase 3 study showed in results reported in June that the mRNA-based flu vaccine was about 27 percent more effective than Fluarix in adults 50 and older. A separate study evaluating safety and immune response included a 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 from people who have been vaccinated, while efficacy assessments usually involve seeing how well a vaccine protects against cases of the disease.
Moderna waited for review of its flu vaccine to begin before moving its experimental combination flu and Covid-19 mRNA vaccine into the FDA review process, Hoge said. This is now on hold as the company awaits a meeting and further guidance from the agency.
Meanwhile, the combination vaccine is advancing in other countries.
“We expect our first approval to be … probably in Europe this year as well,” Hoge said. “So this will be a landmark event.”
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