The vaccine maker Moderna said on Tuesday that the Food and Drug Administration had notified the company that the agency would not review its mRNA flu vaccine, the latest sign of federal health policy that has become hostile to vaccine development.
Dr. Vinay Prasad, the agency’s top vaccine regulator, rejected the company’s application for approval over a concern that Moderna’s clinical trial had compared its experimental vaccine against a product the agency did not consider the best on the market. People in the comparison group received Fluarix Quadrivalent, a flu vaccine sold by GSK.
Moderna had spent years and hundreds of millions of dollars testing its flu vaccine, enrolling 41,000 people and aimed at a market of adults ages 50 and older. The company concluded that its shot was superior to GSK’s product.
Stephen Hoge, the company’s president, said in an interview on Tuesday that the new flu vaccine was designed to be better tailored for a single nation than the ones that tended to be used by an entire hemisphere. He also said the F.D.A. had earlier indicated support for the company’s study plan.
“This refusal to start a review is all confusing, to say the least,” Mr. Hoge said, adding: “It is surprising, and we’re trying to understand what has changed.”
A spokesman for the Department of Health and Human Services, which oversees the F.D.A., said the agency did not comment on communications with individual applicants for drug approval.
Moderna said it had received what is known as a “refuse to file” letter from the agency, meaning that the company tried to submit an application for approval, but was dismissed. Such cursory rejections are unusual; the agency tends to complete a thorough review before denying approval.
Moderna said the agency’s letter did not cite any specific concerns about the product’s safety or effectiveness. A journal article published by company scientists last year concluded that the vaccine was safe. It reported that some of the company’s research showed that the vaccine had generated strong immune responses against both the A and B strains of the flu, though some results indicated that the vaccine seemed to work better against the A strain of the flu rather than the B strain.
A strains of the flu tend to cause more flu cases and more severe illness than B strains do.
This latest move by the F.D.A. reflects expansion of a new policy under Health Secretary Robert F. Kennedy Jr., who has repeatedly criticized the mRNA technology used most successfully against Covid and made by both Moderna and Pfizer. Recognized with a Nobel Prize in Physiology or Medicine in 2023, the technology instructs the body to produce a fragment of a virus that then sets off the body’s immune response.
But Mr. Kennedy has scuttled the use of mRNA in vaccines and canceled hundreds of millions of dollars in funding for research using the technology, claiming it is not safe or effective. During his first year as health secretary, he has quashed several projects involving the technology, including an effort by Moderna to develop a shot against bird flu.
Pfizer has been in a race with Moderna to develop an mRNA flu vaccine. However, Dr. Marty Makary, the F.D.A. commissioner, has alluded critically to Pfizer’s vaccine, saying in news media interviews that it failed to work in seniors in a clinical trial and suggesting it would not pass agency muster.
Moderna spent years on the studies for a vaccine that was meant to improve on egg-based and other methods to combat the flu, allowing nations to specifically select the strain they hoped to target.
Mr. Hoge said the company met with the F.D.A. about the study and understood that the decision of which vaccine to use in comparison would be acceptable, albeit a “review issue,” he recounted. He said the company had requested an additional meeting with the agency about its decision to reject the application.
Mr. Hoge said Blackstone, the private equity company, had invested $750 million in the development of Moderna’s flu shot, in addition to the vaccine maker’s own support for the large clinical trial.
No country has approved an mRNA flu vaccine, although Mr. Hoge said Moderna’s product was being reviewed in Europe, Canada and Australia.
Dr. Prasad’s letter to Moderna said the reason for the refusal was that the company had not run an “adequate and well-controlled” study but had compared its product with a flu vaccine that “does not reflect the best-available standard of care.”
In recent months, Dr. Prasad has held drug companies to standards that were different from what they were expecting based on previous agency guidance, generating backlash from the biotech and pharmaceutical industries. In November, a long list of biotech investors and chief executives wrote a letter of concern about “decisional volatility” and turmoil at the F.D.A.
Dr. Makary has defended Dr. Prasad’s decisions and said the agency’s drug approvals last year were in line with recent years.
In a large clinical trial, Pfizer’s experimental mRNA vaccine against the flu was found to be at least as good as a comparison product against A strains of the flu, but not against B strains. Funded by Pfizer, the study compared the company’s experimental vaccine against Fluzone, a shot on the market sold by Sanofi.
In an interview on “Fox & Friends” in November, Dr. Makary criticized Pfizer’s data, though he did not name the company. “We’re not just going to rubber-stamp new products that don’t work, that fail in a clinical trial,” he said. “It makes a mockery of science if we’re just going to rubber-stamp things with no data.”
In another interview the next month with NPR, Dr. Makary suggested that Pfizer’s vaccine did not meet the agency’s criteria for approval. “I personally like mRNA technology. But this mRNA flu shot in its randomized control trial in seniors failed. It showed no benefit,” he said.
He added: “Well, we basically said, We’re not interested in approving a drug that has failed in its Phase 3 randomized trial.”
Pfizer did not immediately return a request for comment on Tuesday.
Perhaps no vaccine developer has been harder hit than Moderna, as federal health officials have turned against mRNA technology and some vaccines. Demand for the company’s Covid vaccine has declined considerably, after generating huge sales at the height of the pandemic. The F.D.A. also narrowed approval of Covid shots for the season that began last fall. Moderna’s stock has plummeted by more than 90 percent since its peak in August 2021.
Moderna has said it is halting plans for late-stage studies of some experimental vaccines aimed at preventing infectious diseases and infections that lurk in the body. Late-stage studies of Moderna’s experimental cancer vaccines are expected to continue unimpeded.
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