The FDA's biologics center is the most consequential job in American medicine that most people have never heard of. It decides whether gene therapies, vaccines, and rare-disease treatments ever reach patients. And right now, it doesn't have a permanent director.
Vinay Prasad will leave the Center for Biologics Evaluation and Research at the end of April, departing for the second time in under a year, according to Endpoints News. The search for his replacement is narrowing, according to sources familiar with the process. But the candidates face a strange arithmetic: the person widely seen as most qualified was forced out by the same administration now doing the hiring.
Peter Marks ran CBER for nine years. He helped build the system that allowed COVID vaccines to move at unprecedented speed. He was the FDA official who overruled his own staff in 2024 to approve Sarepta Therapeutics' gene therapy for Duchenne muscular dystrophy, a decision that split the scientific community but gave parents a treatment they had been pleading for. In March 2025, Health and Human Services Secretary Robert F. Kennedy Jr. told him to resign or be fired, according to Reuters. Marks chose the first option. His resignation letter said Kennedy's department had made clear that "truth and transparency are not desired by the Secretary, but rather he wishes subservient confirmation of his misinformation and lies." By October, he was running infectious disease research at Eli Lilly.
He is now the leading candidate to return, according to people familiar with the discussions. Which raises a question nobody in official Washington seems eager to answer: what does it mean when the same administration that forced out its top vaccine regulator is now hoping to rehire him?
The instability at CBER goes beyond one appointment. The FDA's drug evaluation center has had five different directors since January 2025, with Tracy Beth Hoeg now serving as acting director. Prasad himself held the CBER job twice, quitting in July 2025 over a dispute about a Duchenne therapy, then returning two weeks later after the White House intervened. He departs again in a few weeks. Investors call this the core problem.
In a survey conducted by RBC Capital Markets, biotech funds ranked regulatory uncertainty as the biggest threat to the sector. An April letter to President Trump from a coalition of nearly 100 rare-disease patient groups, biotech executives, and investors put a number on it: 84% of investors surveyed said they had reduced, paused, or exited rare-disease programs because of FDA unpredictability. Two-thirds of companies said they had grown more cautious about fundraising. The letter urged the administration to "restore regulatory clarity" before the new CBER director takes over.
The data behind the anxiety is stark. In 2025, CBER approved five orphan drugs and issued four rejection letters, turning away roughly half of late-stage rare-disease programs. The historical rejection rate had been closer to 10%. In the first quarter of 2026, CBER approved one orphan drug and issued two rejections, while the drug evaluation center handled eight approvals in the same period.
Some companies describe a more complicated picture. Rezolute, a biotech working on a therapy for a rare form of hyperinsulinism, said the FDA was unusually collaborative in redesigning its Phase 3 trial after early data looked different than expected. CERo Therapeutics described the agency as responsive when it asked to expand a trial into a new indication. Both experiences run counter to the broader narrative of an agency gone rigid. The distinction may be context: early-stage feedback from FDA technical staff has generally stayed constructive, while late-stage regulatory decisions have produced the most visible friction.
The policy shifts during Prasad's tenure are real and, in some cases, potentially lasting. The FDA's default position now favors a single pivotal trial combined with confirmatory evidence rather than two large Phase 3 studies. A new "plausible mechanism" pathway aims to streamline approval for individualized gene therapies for ultra-rare diseases, targeting conditions affecting single patients where randomized trials are impossible. The agency has proposed creating a clinical trial notification system that would replace the existing IND application process for early-phase studies, a change that could compress the timeline for getting a first-in-human therapy into the clinic.
But those reforms were announced via New England Journal of Medicine op-eds and social media posts rather than formal guidance documents, per FDA Insider. Companies say they are watching the actions, not the announcements. Moderna submitted an application for an mRNA flu vaccine that should have fit the agency's stated criteria. The FDA initially refused to file it, according to FDA Insider. The White House intervened. The application was eventually accepted. The episode became a parable about what "flexibility" means when the people saying it and the people deciding it may not be the same people.
For the next CBER director, the agenda is not empty. The plausible mechanism framework needs operational definition. The single-trial standard needs formal guidance. A clinical trial notification pathway needs to move from proposal to reality. And somewhere in that queue of undone policy, there are patients with rare diseases who have run out of time to wait for the FDA to figure out what it wants.
Makary has said he will name a replacement before Prasad leaves. The leading candidate is a man who was escorted out eight months ago. Whether he would accept the job, whether the administration would offer it, and whether the agency can recruit anyone else willing to inherit this particular mess are questions that nobody in the building seems confident answering.
