The U.S. Food and Drug Administration has declined to accept Moderna’s application to review its first mRNA seasonal flu vaccine, the company said Tuesday, in another blow to the technology that has been a target of some Trump administration health officials.
The agency told Moderna that its application did not include an “adequate and well-controlled” trial because the control arm did not reflect “the best-available standard of care in the United States at the time of the study,” according to a Feb. 3 letter posted online by Moderna. It did not identify any safety or efficacy concerns, the company said.
Moderna said the denial was inconsistent with the agency’s previous response and that it had requested a meeting with FDA officials to understand how to proceed.
“The complete surprise here is that at no point did anyone say it wasn’t sufficient to run its clinical trials the way it discussed with the agency,” Moderna’s president, Dr. Stephen Hoge told CNN on Tuesday.
The US Department of Health and Human Services said “FDA generally does not comment on regulatory communications to individual sponsors.” It is rare for the FDA to issue a “refuse-to-file” letter; A 2021 study of nearly 2,500 applications submitted to the agency found that only 4% received such letters.
Moderna used a standard-dose seasonal flu vaccine called Fluarix as a comparator in a clinical trial of 40,700 people to show 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.
Moderna added that as recently as August, in a meeting before submitting its application for approval of the vaccine, the FDA suggested it review the filing and evaluate issues with a comparator during that process. The agency noted that there may be “significant issues” with the data “during review” of the application, according to a written response shared by Moderna.
But last week, the agency declined to review it, according to the letter. It was signed by Dr. Vinay Prasad, director of 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 that the Covid-19 vaccine had killed 10 children and that the agency would change the vaccine approval process.
Moderna is one of three manufacturers of approved Covid-19 vaccines in the US, along with Pfizer and Novavax. Vaccines from Moderna and Pfizer 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 key achievement of Trump’s first term, his second administration has withdrawn support for mRNA technology in infectious diseases. HHS in August canceled 22 projects worth nearly $500 million focused on mRNA vaccine development, claiming against evidence that “these vaccines fail to effectively protect against upper respiratory infections such as COVID and the flu.”
The Covid-19 vaccine is 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 areas where different strains circulate and lead to combinations with Covid-19 vaccines so that people only need one shot to protect against both viruses.
With currently accepted technology, experts select flu strains for each fall’s seasonal vaccines the previous February. Hoge points out that mRNA vaccines can be manufactured very quickly; He said the design for the covid-19 vaccine to be shipped by August is set for May or June.
Selecting strains closer to the start of the flu season can potentially result in a better match to circulating viruses, “and a better match equals, in general, better protection,” Hoge said.
Moderna’s Phase 3 study reported results in June that showed the mRNA-based flu shot produced an effectiveness that was about 27% greater than Fluarix in adults 50 and older. A separate trial evaluating safety and immune response compared the high-dose flu vaccine in people age 65 and older and showed superiority, Moderna said.
Immune response is evaluated in the laboratory by analyzing blood samples from vaccinated individuals, while efficacy evaluations typically include how well the vaccine protects against cases of the disease.
Moderna was awaiting the start of a review of its flu shot before moving its experimental combination flu and Covid-19 mRNA vaccine into the FDA review process, Hoge said. That is now on hold as the company awaits a meeting and further guidance from the agency.
Meanwhile, combination vaccines are advancing in other countries.
“We hope to have our first approval … probably in Europe, and this year,” Hoge said. “So that would be a milestone event.”
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