FDA Rejects Filing and Cites Study Design Issues
The US Food and Drug Administration refused to accept Moderna’s application to review its first mRNA seasonal flu vaccine. The company confirmed this decision on Tuesday. The refusal marks another setback for mRNA vaccine development in the United States. Some health officials in the Trump administration have recently criticized the technology.
The FDA said the application lacked an adequate and well-controlled trial. The agency argued that the control arm did not reflect the best available standard of care in the United States during the study. Moderna said the agency did not raise any safety or efficacy concerns.
Moderna Challenges FDA’s Decision and Seeks Clarification
Moderna said the refusal contradicted earlier feedback from the agency. The company requested a meeting with FDA officials to clarify the next steps.
Moderna President Dr. Stephen Hoge said the agency never indicated that the trial design was inadequate. He said the company followed the trial approach that regulators had discussed.
Rare Regulatory Move Draws Attention
The US Department of Health and Human Services said the FDA generally does not comment on regulatory communications with individual sponsors. Analysts noted that the FDA rarely issues refuse-to-file letters. A 2021 study found that only 4% of nearly 2,500 applications received such letters.
Trial Used Standard Flu Vaccine as Comparator
Moderna used the standard-dose flu vaccine Fluarix as a comparator in a clinical trial involving 40,700 participants. The company said the FDA agreed with that approach in April 2024. Regulators suggested adding data comparing the vaccine with a high-dose flu vaccine for older adults. Moderna said it included that data.
FDA Feedback Shifted Before Filing
Moderna said the FDA suggested in August that it would review the filing and address comparator issues during the review process. The agency warned that the data could pose a significant issue during review.
The FDA later refused to conduct the review altogether. The letter was signed by Dr. Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research, which oversees vaccine regulation.
Leadership Background Fuels Debate
Prasad criticized the government’s Covid-19 response before joining the FDA under Health Secretary Robert F. Kennedy Jr. He claimed last year that Covid-19 vaccines caused deaths in 10 children but did not provide details. He has said the agency will change its vaccine approval process.
mRNA Vaccine Industry Faces Policy Headwinds
Moderna is one of three approved Covid-19 vaccine manufacturers in the United States. Pfizer and Novavax are the other companies. Moderna and Pfizer use mRNA technology for their vaccines. Pfizer also develops mRNA-based flu vaccines.
The Trump administration previously supported rapid mRNA vaccine development during the pandemic. The second Trump administration withdrew support for mRNA research in infectious diseases. The Department of Health and Human Services canceled 22 mRNA vaccine projects worth about $500 million in August. Officials claimed these vaccines do not protect effectively against upper respiratory infections like Covid-19 and flu.
Scientists Highlight mRNA Vaccine Benefits
Experts estimate that Covid-19 vaccines saved millions of lives. Researchers hope mRNA technology can improve seasonal flu vaccines. Scientists believe the technology can enable regional tailoring and combination shots for flu and Covid-19.
With current methods, experts select flu strains for seasonal vaccines in February. Hoge said mRNA vaccines can be manufactured much faster. He said Covid-19 vaccine designs were decided in May or June and shipped by August.
Choosing strains closer to flu season could improve matching with circulating viruses. Better matching usually means better protection, Hoge said.
Trial Results Showed Higher Efficacy
Moderna’s phase 3 study showed the mRNA flu shot achieved about 27% higher efficacy than Fluarix in adults aged 50 and older. A separate trial comparing the vaccine with a high-dose flu shot for people aged 65 and older showed superior results, Moderna said.
Scientists assess immune response by analyzing blood samples from vaccinated participants. Researchers assess efficacy by measuring protection against disease cases.
Combination Vaccine Plans Now on Hold
Moderna waited for the flu vaccine review before submitting its combined flu and Covid-19 mRNA vaccine for approval. The company paused that plan while awaiting further guidance from the FDA.
The combination vaccine continues development in other countries.
“We expect our first approval probably in Europe this year,” Hoge said. “That will be a milestone event.”
