Marty Makary leaves a mixed legacy as FDA commissioner

The US Food and Drug Administration is once again at a crossroads after Commissioner Marty Makary resigned from his position Tuesday.

President Donald J. Trump signed off on a plan to fire Makary late last week, the Wall Street Journal first reported. Days later, Makary chose to resign, Politico first reported on Tuesday afternoon. Deputy Commissioner Kyle Diamantas, a lawyer who had overseen food regulation at the agency, will serve as acting commissioner.

The departure marks the end of a tumultuous tenure in which Makary—a respected surgeon who was considered one of Trump’s more middle-of-the-road appointments—walked a fine line while trying to appease his boss, Department of Health and Human Services secretary Robert F. Kennedy Jr.; Kennedy’s increasingly fractured Make America Healthy Again (MAHA) coalition; biopharmaceutical-industry leaders; and patients and their families.

In the end, he didn’t quite succeed. “He’s going to go on, and he’s going to lead a good life,” Trump said of Makary during a press conference at the White House on Tuesday. “He was having some difficulty. He’s a great doctor. He’s going to go on and do well.”

When Trump first nominated Makary to head the FDA, a role he started in April 2025, many in the biotech and pharmaceutical world were cautiously optimistic. Compared with other nominees at the time—especially those, including Kennedy, who had promoted conspiracy theories about vaccines—Makary seemed to be a “reasonable choice,” as a biotech executive and investor put it to C&EN at the time. Makary told politicians that he would rebuild trust in public health through science-based evidence, common sense, and transparency.

But after just over a year at the top of the FDA, Makary leaves behind a mixed legacy.

“Hopefully the permanent replacement will be someone who knows what they are doing, like a Scott Gottlieb,” says a biotech executive, referring to an FDA commissioner from Trump’s first administration. The executive asked not to be identified by name to preserve relationships with regulators.

Antipathy to vaccines marked Makary’s tenure

One of Makary’s first actions as commissioner was to publish new guidance for annual COVID-19 boosters, indicating that going forward, the shots would be authorized only for people 65 years old and older and those at risk for health complications. Makary and Vinay Prasad, then the director of the Center for Biologics Evaluation and Research (CBER), published the new guidance apparently without input from FDA staff and without convening the FDA’s vaccine advisory committee, skirting normal processes for making changes to drug approvals. The guidance created confusion around eligibility and insurance coverage.

And the hand-wringing over vaccines under Makary wasn’t limited to COVID-19. The FDA also refused to review a messenger RNA–based flu shot made by Moderna, then backtracked that decision. In the last month, agency leaders have also blocked the publication of studies showing that COVID-19 vaccines and a shingles vaccine are safe and effective, the Washington Post recently reported.

“The current uncertainty in the US FDA regulatory environment creates real challenges for businesses, patients, and the broader innovation ecosystem,” Moderna CEO Stéphane Bancel told investors on an earnings call in February, after the FDA initially refused to review his company’s flu-vaccine application. “When expectations and review timelines are unpredictable, companies face greater risk and can hesitate to invest, slowing the development of breakthrough medicines.”

Twelve former FDA commissioners published an editorial in the influential New England Journal of Medicine in December, expressing concern over the agency’s policy on vaccines and the potential threat to public health.

Biopharma leaders such as Bancel lost trust with Makary’s FDA over time. FDA reviewers repeatedly failed to meet deadlines on drug-approval decisions, apparently due to staff cuts enacted by the short-lived Department of Government Efficiency, or DOGE—Elon Musk’s cost-cutting initiative, not an official executive branch. Makary, who was confirmed as commissioner shortly after those cuts, publicly denied that these delays were happening.

“Dr. Makary inherited an FDA in crisis after the DOGE changes, which included the firing of thousands of employees. These staffing and morale challenges were compounded by constant leadership changes over the past year and questions around shifting FDA standards for drug approvals,” the president and CEO of the Biotechnology Innovation Organization, John F. Crowley, says in a statement on Makary’s resignation.

In a statement emailed to C&EN, Stephen Kent, media director of the libertarian advocacy group Consumer Choice Center, blames Makary for “hundreds of millions lost in the biotech sector as approval processes for drugs slowed down by 14% from 2024.”

“Real patients die waiting for new treatments to come to market, and it looks like Trump has had enough,” Kent says.

Delayed decisions, unpredictable requirements at the FDA

Makary enacted multiple programs that were meant to speed up drug reviews but so far have yet to deliver on that promise. In fact, the FDA approved fewer new drugs in 2025 than in 2024. He pushed the agency to rapidly adopt artificial intelligence tools for product reviews last year, and he announced this year that the FDA would default to accepting a single clinical trial, rather than two. He rolled out the Commissioner’s National Priority Voucher (CNPV) program, designed to award recipients with an expedited review if they meet at least one of the agency’s national priorities. But the program has proved controversial; agency reviewers were reportedly blocked from voting on at least one drug approval under the program. And the vouchers don’t necessarily translate to a faster drug approval: the FDA rejected an early voucher recipient from a fast-track approval pathway in February.

Similarly, a new framework for individualized medicines, championed by Makary, has met roadblocks, Stat News reported in March. Called the plausible mechanism pathway, the framework is meant to streamline the process of tweaking bespoke therapies for new patients. But already, researchers have hit snags with higher-than-expected standards for manufacturing and quality control.

While he publicly said he wanted more regulatory flexibility, Makary oversaw an agency that at times arbitrarily tightened or loosened its standards for data. The pharmaceutical firm UniQure said in November that the agency had surprised executives by asking for more clinical research for a Huntington’s disease drug candidate; prior to Makary’s arrival, the agency had greenlit a biologics license application based on a Phase 1/2 clinical trial that was ongoing. Conversely, the agency approved leucovorin for a rare disease called cerebral folate deficiency without any clinical trial data, though it stopped short of approving the same drug for autism, which MAHA activists wanted.

Makary’s promises of radical transparency also largely did not come to fruition. Despite his purported wishes to increase drug safety monitoring, for instance, the DOGE-driven layoffs hindered the FDA’s ability to perform inspections and risk evaluations early on in Makary’s tenure. Advisory committees, meanwhile, met infrequently, despite their longstanding status as a public forum meant to increase the transparency of agency decisions.

Makary’s departure is the latest in a long string of high-profile exits from Trump’s FDA. Prasad, the former CBER director, was forced out, then brought back, before he left a second time toward the end of April. The Center for Drug Evaluation and Research meanwhile lost multiple directors in the past year, including George Tidmarsh and Richard Pazdur.

Laurel Oldach contributed reporting.