FDA CBER Chief Marks overrules staff drug reviewers 'with trepidation'

Peter Marks, M.D., Ph.D., says he trusts staff reviewers at the FDA, who do “incredibly great work”—but sometimes decisions about efficacy require a broader view.

“Why would I be there if everything was 100% perfect?” the head of the agency’s Center for Biologics Evaluation and Research said in an interview with Fierce Biotech. 

Marks’ comments come about a month after the FDA granted accelerated approval to Sarepta’s gene therapy for four and five-year-old patients with Duchenne muscular dystrophy. The decision was at odds with agency reviewers who said ahead of an advisory meeting to discuss the treatment that the available data did not provide "unambiguous evidence" of clinical benefit.

Marks wrote in a memo after the fact that he disagreed with the reviewers’ assessment of the efficacy in that age population and came to “a different conclusion."

Defending his authority to do so—though not speaking specifically about the Sarepta decision—Marks told us that one of the benefits of being in his role at the agency is that he can assess approval submissions without “the baggage of perhaps the back and forth” between reviewers and drug developers. 

“My opinion is generally the reviewers are right,” he said. “And I do contradict them or overrule things with trepidation.” 

Marks also said candidly that as a center director at the agency, he’s more willing to take risks than staffers, saying that it’s “natural as a regulator to be somewhat conservative.” 

“I know that in some of the decisions that I've made, it's possible that I'll be wrong,” Marks said. “But I can live with that in the bigger picture of knowing that it's important for us—for the community to know—that we're not so dead set on getting it right 100% of the time that we actually prevent things from getting to market that could potentially help people a bit sooner.” 

“My opinion is generally the reviewers are right,” he said. “And I do contradict them or overrule things with trepidation.” 

Safety data is a red line for Marks, however. He asserted that he would never overrule reviewers if there were questions about safety. Sarepta’s gene therapy, for example, had 13 serious side effects in 85 patients but no deaths or discontinuations due to the treatment. Duchenne advocates who spoke at advisory hearings for the therapy were emphatic that the side effects were dwarfed by the risk of disease progression. 

Marks’ Sarepta ruling has, so far, caused much less consternation than the agency’s decision, backed by the Biden administration, to recommend a first round of booster doses to all eligible Americans in the fall of 2021. The decision, relayed in a joint statement from top health officials in August 2021, caused internal dissent and spurred the departure of two top deputies, Marion Gruber, Ph.D., and Phil Krause, M.D. The two scientists penned an editorial in the Lancet a couple of weeks after their planned departures were announced arguing that evidence at the time didn’t support boosters in the general population.