For years before he became director of the Food and Drug Administration's Center for Biologics Evaluation and Research, epidemiologist Vinay Prasad openly railed against what he perceived as the shoddy design of drug trials and the deference regulators gave them, sending biotech stocks tumbling when Commissioner Marty Makary appointed him.

A vaccine maker that hit the federal jackpot during COVID-19 acted caught off-guard when the former University of California San Francisco medical professor put his gripes into practice, halting its FDA application for a new mRNA flu vaccine based on what he considered weak trial design.

Moderna accused Prasad, who described his predecessor Peter Marks as a "bobblehead" for drug approval, of changing the rules in the middle of the game by refusing to review its biologics license application (BLA) without citing "specific safety or efficacy concerns."

Prasad's Feb. 3 "refusal to file" letter – which Moderna posted a week later on its COVID resources page for some reason – says the FDA warned the company before it even started the mRNA flu trial that the proposed design raised red flags.

"CBER does not consider the application to contain a trial 'adequate and well-controlled' and the application is therefore, on its’ [sic] face, inadequate for review," because the control arm "does not reflect the best-available standard of care in the United States at the time of the study," Prasad said, which was "consistent with FDA's advice" before the study.

This was just the agency's "preliminary review of the application and is not indicative of deficiencies that would be identified later," when the FDA conducts a "substantive review," Prasad emphasized, implying fresh hurdles for Moderna even if it runs a new trial.

Moderna CEO Stéphane Bancel responded with his own thinly veiled threat against Prasad, who had already left the administration once under assault from populist and corporate conservatives who blasted his avowed support for progressive policies and more regulation before Prasad joined the administration. 

CBER's decision, which Bancel reiterated "did not identify any safety or efficacy concerns with our product, does not further our shared goal of enhancing America's leadership in developing innovative medicines," said the billionaire Frenchman, who came to Boston-based Moderna from French diagnostics company BioMerieux.

"We look forward to engaging with CBER to understand the path forward as quickly as possible so that America's seniors, and those with underlying conditions, continue to have access to American-made innovations," Bancel said, hinting the company would take jobs overseas if the FDA continued its current trajectory.

Department of Health and Human Services spokesperson Andrew Nixon told Just the News Moderna ignored "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 company gave trial participants 65 and older "a substandard of care against the recommendation of FDA scientists" by using standard-dose vaccines, rather than "a subset of high dose flu shots," as the control in their trial, thus exposing them to an "increased risk of severe illness," Nixon wrote in an email. He didn't answer a followup seeking the FDA's written communications cited in Moderna's press release.

Moderna spokesperson Chris Ridley told Just the News it had "produce[d] in the press release the relevant language from FDA" when asked for those written communications.

"The industry depends on clear, transparent rules that are applied consistently in order to make the long-term investments that benefit Americans," Ridley wrote in an email when asked why Moderna wouldn't calibrate the study in light of Prasad's reputation as a stickler for trial design.

"In this case, the FDA reviewed and cleared the trial design as adequate before the study began 18 months ago. Then in August of 2025, upon success of the trial, the FDA indicated the use of comparator – which is worth noting is an FDA approved vaccine – would be a point of discussion during the review period," he said. "Now, however, they have refused to even have that discussion."

'A more potent control might have narrowed or erased the efficacy gap'

"Comparing a new vaccine only to a weaker, non-preferred option creates a biased yardstick," Institute for Pure and Applied Knowledge founder and CEO James Lyons-Weiler, a former University of Pittsburgh senior research scientist, wrote in an analysis of the dispute.

The study design "inflates the apparent relative benefit and fails to show whether the new product is truly an advance over the vaccines that seniors should be receiving today," he wrote. "A more potent control (like Fluzone High-Dose) might have narrowed or erased the efficacy gap that Moderna observed."

The publication of the RTF letter crashed a Moderna stock rally earlier in the day, Feb. 10, dropping its share price 10% in after-hours trading, according to Seeking Alpha stock analyst Stephen Ayers, who said it reiterates why he lists Moderna as "sell."

"While I believe the FDA is in 'the wrong' for issuing an RTF instead of just reviewing the data and asking for more, comparing a new-age mRNA vaccine to an older, weaker standard-dose vaccine for seniors – even if deemed acceptable – may have understandably come off as scientifically lax," Ayers wrote.

Drugmakers had a friendly relationship with Prasad's predecessor, Marks, who overruled FDA career scientists and advisers to first approve, then expand a pediatric gene therapy, whose distribution Prasad pressured its maker to halt in the wake of three deaths.

Days after Sarepta Therapeutics paused Elevidys last summer, President Trump whisperer Laura Loomer attacked Prasad as a "leftist saboteur," followed by The Wall Street Journal editorial board dubbing him a "Bernie Sanders Acolyte in MAHA Drag." 

The FDA quickly lifted the hold, and the White House threw Prasad under the bus, prompting his resignation, but Makary coaxed Prasad back less than two weeks later. By Thanksgiving, Prasad was flexing again, imposing stricter guidelines for vaccine approvals after the agency confirmed 10 children died “after and because of” receiving a COVID vaccine.

Shortchanging trial design means losing 'at least' two flu seasons

The only FDA document provided in Moderna's press release is Prasad's 2-page RTF letter, though the company quotes from others it did not provide.

Following Moderna's submission of the Phase 3 trial protocol in April 2024, CBER's "written guidance" said it would be "acceptable" for the company to "use a licensed standard dose influenza vaccine as the comparator," but the agency "recommend[s]" using high-dose vaccines among participants 65 and up, according to Moderna.

The latter are "preferentially recommended for use in older adults," and the data on "comparative efficacy" of Moderna's new vaccine against these high-dose vaccines "may help inform" the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices' recommendation for the new vaccine in older people, the guidance said.

"If you proceed with using a standard dose influenza vaccine comparator in participants ≥65 years of age, we agree with your plan to include statements in the Informed Consent Form," CBER said, according to Moderna. 

The company said it had a "pre-submission" meeting with CBER in August 2025 after the Phase 3 efficacy trial met "all agreed upon pre-specified primary endpoints." 

The "written feedback" from CBER asked for "supportive analyses on the comparator" in Moderna's submission, indicating the data would be a "significant issue" for the BLA, and Moderna complied by providing data from a separate Phase 3 trial comparing the new vaccine against "a licensed high-dose influenza vaccine."

Prasad's RTF letter was the first time CBER frowned on the "adequacy" of the trial in nearly two years of back-and-forth, Moderna said. 

"It should not be controversial" to use "an FDA-approved vaccine as a comparator," which CBER "agreed on" before the trial started, Bancel said.

Lyons-Weiler, the IPAK CEO, emphasized that Moderna had "ethical and practical considerations" in what to use as a comparator, given that high-dose vaccines weren't recommended for middle-age adults when it planned its studies, and that the FDA "initially acquiesced" to this "middle path."

The problem is its "headline claim" that the mRNA shot was 26.6% more effective than the standard jab – comparable to "what prior enhanced vaccines achieved over standard-dose products" – comes from a trial that "pooled adults 50 and over, using a suboptimal control for those over 65," undermining its "clinical significance," Lyons-Weiler wrote.

Seeking Alpha's Ayers said Moderna didn't seem to appreciate there's a new sheriff in town with higher standards and underestimated the "bumpiness" it would face.

By not comparing "a vaccine to the best version currently given to that specific group," Moderna is likely to miss "at least two influenza seasons" and lose ground against competitors, as it's forced to conduct an outcomes trial against the high-dose vaccine, Ayers said.