Accelerated approval will be ‘the norm’ for gene therapies, FDA’s Peter Marks says

The FDA will increasingly use accelerated approval for gene therapies aimed at rare conditions, according to Peter Marks, the FDA’s top official overseeing cell and gene therapies, the clearest signal yet of how widely the agency will deploy its expedited pathway.

Marks’ comments, made last week at a workshop in Washington, build on a stance he took last year backing accelerated approval for gene therapies, which often target young children with ultra-rare conditions.

“If we don’t lean into accelerated approval, we’re going to leave a lot of patients behind,” Marks said during the workshop at the Reagan-Udall Foundation in Washington last week. “Accelerated approval is going to be the norm for a lot of our initial approvals of gene therapies.”

There are more than 10,000 rare diseases, but companies often struggle to bring therapies to market for these conditions due to the small numbers of patients and financial constraints. In recent comments, Marks has indicated that he views accelerated approval as a powerful tool to speed new treatments and ensure that companies don’t give up on promising therapies.

“There are a lot of gene therapies for rare diseases that are almost there,” Marks said. “And it’s a question of, how do we get them across the finish line?”

The agency’s evolving position is part of a wider debate over how to regulate gene therapies, which without regulatory rigor stand to give patients misplaced hope and drain the health system. Confirmatory trials are required as part of the accelerated approval pathway, and typically are randomized controlled trials to verify the clinical benefit. But because these are such small populations with fatal diseases, how these trials are conducted will need to be tweaked given that it would be unethical to run placebo-controlled trials in some of these populations.

The bullish comments from Marks also show how CBER is eager to look at new biomarkers, even if they’re not yet qualified, to condense what would normally be a multiyear approval process. Marks, who announced on Monday that he’s also now the chair of the FDA’s new accelerated approval council to help advance reforms around the accelerated pathway, made clear that the use of biomarkers that have yet to be qualified is already common, and it is not a requirement ahead of an accelerated approval.

“There are plenty of biomarkers that have been used over the years” that were not qualified, he told the workshop. “As long as you can show that you have a biomarker that can be measured accurately and reproducibly, we don’t necessarily always need all of the additional work that gets to qualification,” he said.

Gavin Imperato of CBER’s Office of Clinical Evaluation told the workshop that the regulatory system must evolve with the science, “and that’s the reason why we’re leaning into biomarkers and accelerated approval” in these cases of gene therapies.

“I totally understand the frustration. But regulatory review is a human enterprise, so we do approach drug development with a tremendous amount of empathy,” he said.

Last June, Sarepta won an accelerated approval for its Duchenne gene therapy, but Marks said Monday at a separate event that its approval shouldn’t be viewed as typical, though he’s previously pledged to expand the therapy’s label despite a failed confirmatory trial.

John Crowley, who will take over next month as the next CEO of industry group BIO, took issue with the idea that FDA is using flexibility or lowering the bar for some of these rare disease treatments.

“We have at least 200 rare disease programs that have stopped,” Crowley said. “We have so much hope and promise and we’re getting in our own way.”

Ultragenyx CEO Emil Kakkis explained to Endpoints News in an interview that he’s developing an AAV gene therapy that’s shown it can lead to rapid and decreased levels of heparan sulfate in cerebrospinal fluid in patients with Sanfilippo syndrome type A (MPS IIIA). He said he hopes the therapy will win approval in 2025, but Ultragenyx — which co-sponsored the workshop with Denali Therapeutics, Orchard Therapeutics and Regenxbio — has not yet submitted an application.

“It’s a bold statement from the CBER head” on the use of the accelerated approvals, “but I think what he’s saying is, we cannot let this go and we need to move forward. We need to get going,” Kakkis said.

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