The FDA issued a rare Refusal-to-File letter to Moderna over its mRNA-based influenza vaccine application, in an unusual move that sent the biotech’s shares tumbling.
The FDA’s stunning decision to decline even a glance at Moderna’s application for an mRNA-based influenza vaccine has roiled an already weary biopharma industry.
The Refusal-to-File letter released on Tuesday stated that the agency would not even review Moderna’s application for the flu vaccine mRNA-1010, based on faults the agency found with the package Moderna submitted.
The letter arrived after a year of dramatic regulatory reversals that have left biopharma companies spinning. That includes the surprise rejections of Replimmune’s melanoma drug and Capricor’s Duchenne muscular dystrophy cell therapy. The last decision reportedly followed internal arguments about the application and ultimately resulted in two high-ranking FDA officials, Nicole Verdun and Rachael Anatol, beingput on leave. Both have since left the agency.
That Moderna’s letter happened at all is surprising. But there were a few more reasons the FDA’s rejection was especially jarring, particularly in light of the agency’s new and tightening regulations around vaccines in the U.S.
1. RTFs Are Rare and Reserved for Incomplete Applications
RTFs are typically used in cases where sponsors submit drug applications that are incomplete in some way. That could mean the application was administratively incomplete, with required parts of the application omitted, or it could be scientifically incomplete, lacking “critical data, information or analyses needed to evaluate safety, purity and potency or provide adequate directions for use,” according to the FDA’s guidelines for RTF usage.
The FDA usually issues just a handful of these rebukes every year. A 2021 JAMA Internal Medicine study found that in the 10 years between 2008 and 2017, the FDA received about 2,400 applications and issued 98 RTFs, a 4% overall rate.
Axsome Therapeutics got one in June 2025, over issues with how well controlled a trial was for the fibromyalgia treatment AXS-14. Axsome initiated a new trial to shore up the application. ImmunityBio got an RTF in May 2025 for bladder cancer drug Anktiva and immediately decried the letter as “inconsistent” with guidance the company had received at a meeting with the FDA. The company requested a Type A meeting with the agency and has since met with the agency to discuss the application.
In the Moderna RTF, the FDA’s Center for Biologics Evaluation and Research (CBER) said that the company failed to support the mRNA-1010 application with an “adequate and well-controlled trial.” The letter states that Moderna used an approved standard-dose flu shot as a comparator, and that “does not reflect the best-available standard of care.” Because of that, the FDA deemed the application “not sufficiently complete to enable a substantive review.”
2. CBER Head Vinay Prasad Personally Signed the Letter
In past RTFs gathered by the 2021 study, the head of the suboffice within the FDA that covers the specific area the drug addresses is typically the person signing off on the rejection. A 2017 RTF issued to Mayne Pharma for the anti-fungal medication itraconazole was signed by Sumathi Nambiar, the director of the Center for Drug Evaluation and Research’s Division of Anti-Infective Products, for example.
In Moderna’s case, CBER head Vinay Prasad, who has been a vocal critic of vaccine regulations, handled the letter himself, instead of CBER’s Office of Vaccines Research and Review director David Kaslow. And he reportedly overruled Kaslow and other FDA staffers in doing so, as they deemed Moderna’s application worthy of review, three agency officials familiar with the matter told STAT News.
3. Moderna Published the Letter Itself
In the past, the contents of RTFs have been kept secret. The 2021 JAMA study accessed the FDA’s internal database to perform its analysis. Instead, Moderna went on the offensive, publishing the letter in redacted form. The company argued that the RTF contradicted other communications Moderna has had with the FDA saying that a standard-dose flu shot was acceptable.
It is still unclear what comparator group Prasad wants Moderna to use. In May 2025, the Department of Health and Human Services announced a new policy requiring that vaccines be tested against placebo in clinical trials. However, flu vaccines were supposed to be an exception to that rule, since flu vaccines “have been tried and tested for more than 80 years,” according to the agency.
The FDA last year began publishing Complete Response Letters, rejections that the agency issues after completing a full review of a drug application, but to date has not been publishing RTF letters. While it’s possible the FDA would have eventually released this letter, it would be a change in well-established protocol.
4. Moderna CEO Responds Publicly
Companies have been careful not to draw the administration’s ire. But in recent weeks, some have been speaking out, like Sanofi’s Paul Hudson, Pfizer’s Albert Bourla and now Moderna’s CEO Stéphane Bancel.
“Not everybody looks to the top of the HHS to get people with their guidance on how to live their lives,” Hudson said in a meeting with reporters in January. Bourla called the federal government’s stances on vaccines “almost like a religion” at the World Economic Forum in late January.
In response to the RTF, Bancel did not hide his disappointment. “It should not be controversial to conduct a comprehensive review of a flu vaccine submission that uses an FDA-approved vaccine as a comparator in a study that was discussed and agreed on with CBER prior to starting,” he said in a statement issued by the company Tuesday.
