Moderna Study Rejected by FDA for Inadequate Controls
FDA reversed course and agreed to review Moderna's mRNA flu vaccine application after initially rejecting it over comparator selection.
Objective Facts
In early February 2026, the FDA sent Moderna a rare refusal-to-file letter, refusing to accept the application to review its mRNA seasonal flu vaccine. The FDA stated the application didn't contain an 'adequate and well-controlled' trial because the control arm didn't reflect the 'best-available standard of care'. Moderna used Fluarix, a standard-dose seasonal flu vaccine, as a comparator in a 40,700-person trial, and said the FDA had agreed with that plan in April 2024 but suggested it also include data comparing its vaccine with a high-dose flu vaccine for people over 65, which the company said it did. Prasad overruled career FDA scientists ready to review the application, with the head of the vaccine office having written a memo supporting review. After a February 18 meeting, the FDA reversed course and agreed to advance the application for review, with Moderna CEO Stéphane Bancel stating appreciation for the FDA's constructive engagement.
Left-Leaning Perspective
STAT News reported that the rejection of Moderna's flu shot application is the latest example of Vinay Prasad overruling career FDA scientists to place vaccines under harsher scrutiny, with the moves representing the latest instances of Prasad subjecting vaccines to harsher scrutiny. Science magazine commentators argued this application was being denied by Prasad against FDA experts' recommendation because he and the rest of the Trump administration are hostile to vaccines in general and to mRNA technology in particular, stating 'I don't see how anyone can look at the statements and actions of the political appointees (from RFK Jr. on down) and come away with any other impression'. Dr. Michael Osterholm told PBS that despite the vast majority of FDA staff supporting it, a single individual, Dr. Prasad, decided against approving it, stating 'This sent chills up the spines of all of us in public health and the vaccine world because it's so arbitrary. There was absolutely no basis for which to do this'. According to The Conversation's law professor Ana Santos Rutschman, this is the first time the FDA has tried to preclude the review of a vaccine for reasons that do not have to do with safety or efficacy, and the move signals an escalation in the agency's efforts to intervene in established procedures for testing vaccines under Kennedy's leadership. A CIDRAP editorial noted that the suggestion that a company running a trial under an FDA-approved design was 'rigging' the study is a remarkable departure from regulatory norms, and that both Fluzone High-Dose and Fluad were themselves approved using the same comparator approach that Moderna employed. Left-leaning coverage emphasizes that with vaccine law and policy in turmoil, incentives for vaccine manufacturers are shrinking, and the FDA's move risks fueling further mistrust in vaccines, aligning with a wider push from federal health officials to question long-settled science.
Right-Leaning Perspective
HHS spokesperson Andrew Nixon defended the FDA decision in Fox News and other outlets, arguing the FDA 'rejected Moderna's application for filing because the company refused to follow very clear FDA guidance from 2024' and stating 'Moderna exposed participants age 65 and over to increased risk of severe illness by giving them a substandard of care against the recommendation of FDA scientists'. An unnamed senior FDA official speaking on background characterized the decision as an ethical necessity, stating 'You can either do what's right and give seniors the standard of care that protects them the best. Or you can kind of rig the study so that it makes your product look better. It's bad behavior in my opinion. It's morally problematic. It borders on putting profits ahead of patients'. The FDA official distinguished Moderna's mRNA platform as 'an entirely novel platform' that warrants heightened scrutiny. Amesh Adalja from Johns Hopkins Center for Health Security told Axios that 'It seems that the federal government, at this point, has decided unjustifiably against mRNA vaccines,' though an FDA official countered that the decision was based on study design, not overarching objections to mRNA vaccines, and that Kennedy was 'not directly or indirectly involved'. A senior FDA official stated 'I would like to see more research with mRNA technology. But I don't think the government should pay for it. These companies made over $50 billion on the mRNA COVID shot'. Within FDA leadership, CBER director Vinay Prasad has been a vocal critic of mRNA vaccines who previously called the decision to deprioritize mRNA vaccine technology research 'wise,' citing long-term safety and better alternatives.
Deep Dive
In April 2024, under the Biden administration, Moderna submitted its Phase 3 trial protocol to the FDA's CBER, which responded in writing that using a standard-dose comparator would be acceptable while recommending—but not requiring—a high-dose comparator for older adults. The FDA placed no clinical hold and raised no objections before the trial began enrolling in September 2024. Moderna conducted two Phase 3 studies enrolling over 43,800 participants, with the pivotal efficacy trial comparing mRNA-1010 to a standard-dose vaccine demonstrating 26.6% relative vaccine efficacy, and a separate trial comparing it to a high-dose vaccine showing superiority. The regulatory timeline makes the FDA's decision difficult to defend: In April 2024, CBER responded that standard-dose was acceptable while recommending high-dose. The agency placed no clinical hold and raised no objections before trial enrollment in September 2024. In August 2025, after successful trial completion, Moderna held a pre-submission meeting and CBER flagged the comparator as a 'significant issue during review' and requested analyses, which Moderna provided. However, Prasad personally overruled the FDA's reviewers, with three agency officials telling STAT that career scientists were ready to review the application and David Kaslow, the head of the vaccine office, wrote a detailed memo explaining why the FDA should embark on the review. According to TIME, Prasad made the decision against the advice of FDA staff, who recommended reviewing the application and were prepared to do so. Both Fluzone High-Dose—which Prasad now considers the gold standard—and Fluad were themselves licensed on the basis of trials comparing them to standard-dose vaccines, suggesting that if those products used the same comparator approach now deemed inadequate, the logical consistency of the regulatory standard is questionable. After the FDA's reversal, analyst Mani Foroohar described it as 'regulatory whiplash,' noting the quick reversal could be a 'tailwind for bulls who argue [Moderna] can effectively leverage public pressure against an Agency that has been skeptical of mRNA flu vaccines under current HHS/FDA leadership'. Prasad overruled his own staff in deciding not to review Moderna's application, and refusing to consider the application at all is not the standard course of action for disagreements over study protocols—that's typically the realm of FDA reviews or advisory committee discussions.