FDA Reverses Decision, Will Review Moderna's mRNA Flu Vaccine Application

The Food and Drug Administration reversed course on Wednesday and will now review Moderna's application for the first mRNA-based flu vaccine, less than two weeks after the agency refused to consider it. The decision comes after Moderna requested a Type A meeting with the FDA and proposed a revised regulatory approach.

The FDA sent a "refusal to file" letter to Moderna on Feb. 3 calling its application "inadequate for review." The agency said it wouldn't review the new shot because the company didn't compare it to a high-dose flu vaccine for older people as part of its main clinical trials. Such letters are rare, according to a 2021 study in JAMA Internal Medicine.

Moderna said the FDA had agreed to its study design 18 months ago. According to a company statement, Moderna included data from a separate trial comparing its mRNA shot to a high-dose flu vaccine when it submitted the application. "At no time in the pre-submission written feedback or meeting did [the FDA's Center for Biologics Evaluation and Research] indicate that it would refuse to review the file."

A Health and Human Services Department spokesman said in an emailed statement that "the FDA rejected Moderna's application for filing because the company refused to follow very clear FDA guidance from 2024 to test its product in a clinical trial against a CDC-recommended flu vaccine to compare safety and efficacy."

The FDA commissioner hinted during a Pharmaceutical Research and Manufacturers of America event on Tuesday that the agency's refuse-to-file letter to Moderna wasn't the end for the company's shot. "That letter, in my mind, is part of the conversation where you'll see a dialogue between the company and the agency, and they can always, after that letter, ask for the more detailed review," he said during the PhRMA Forum in Washington, D.C. "But that's part of the process. That's a conversation."

Following the meeting with the FDA, Moderna amended its application. Under the updated approach, Moderna is seeking traditional approval for adults ages 50 to 64 and accelerated approval for adults 65 and older. The company agreed to add a confirmatory study in older adults that will use a high-dose flu shot after the mRNA vaccine is on the market.

"We appreciate the FDA's engagement in a constructive Type A meeting and its agreement to advance our application for review," said the CEO in a statement. "Pending FDA approval, we look forward to making our flu vaccine available later this year so that America's seniors have access to a new option to protect themselves against flu."

The FDA has set Aug. 5 as the target date for finishing its review, which could allow the vaccine to be available before the next flu season begins. The company says the new vaccine will be ready for the next flu season, pending FDA approval.

To test the safety and effectiveness of its mRNA flu shot, Moderna conducted two phase 3 trials. In one trial, more than 40,000 participants got the experimental shot or a standard flu shot. Another trial compared the mRNA vaccine to a standard shot and the high-dose shot recommended for seniors. The dispute centered over a 40,000-person clinical trial that concluded Moderna's new vaccine was more effective in adults age 50 and older than one of the standard flu shots used today.

In the FDA's rare "refusal to file" letter, the vaccine director faulted the trial for not including another brand specifically recommended for people 65 and older. The letter did not express concerns about the safety or effectiveness of the shot, which Moderna intended for use among adults age 50 and older.

Moderna used its mRNA technology to swiftly create and manufacture its COVID-19 shot during the pandemic. The company is hoping to use that technology to make flu shots, too. Using mRNA allows for quicker development of vaccines. While traditional vaccines are based on a weakened virus, mRNA vaccines instead use a molecule called messenger RNA that the body recognizes as foreign. It prompts production of antibodies that allow the body to respond quickly if exposed to the virus itself.

Moderna says the total investment in the shot is over a billion dollars, including up to $750 million from Blackstone, an asset management firm. Moderna's flu vaccine candidate is also under review in Europe, Canada and Australia. Moderna said its new flu shot has been cleared for review in Australia, Canada and the European Union.

The highly unusual public dispute was the latest sign of the FDA's heightened scrutiny of vaccines under the Health Secretary, particularly those using mRNA technology, which he has criticized before and after becoming the nation's top health official. In the past year, FDA officials have rolled back recommendations around COVID-19 shots, added extra warnings to the two leading COVID vaccines — which are made with mRNA technology — and removed critics of the administration's approach from an FDA advisory panel.

In August, HHS canceled nearly $500 million in federal contracts tied to mRNA vaccine development, terminating 22 projects funded through the Biomedical Advanced Research and Development Authority and stating that no new mRNA vaccine initiatives would be approved. In May, the U.S. Department of Health and Human Services pulled funds for Moderna to develop a bird flu vaccine.