CBER Rethinks Clinical Holds Investors Don't Like

May 19, 2023 11:28 AM EDT
Cell/Gene Tx
FDA+
CBER chief Peter Marks to consider 'alternatives' to clinical holds as they 'put shudders down investors' spines'
Zachary Brennan
Senior Editor

As members of the House expressed concerns with the number of clinical holds at Peter Marks’ Center for Biologics Evaluation and Research, Marks said at a conference on Wednesday that there is a way to manage the holds “that’s more user friendly,” noting CBER will work more in advance with sponsors.

Marks acknowledged an uptick in clinical holds for cell and gene therapies during the height of the pandemic, “where we got really resource constrained,” especially taking into account the two-week clock to review new INDs compared with how long it takes for each IND to get to the reviewers.

But Marks stressed that CBER will “help work with the sponsor to resolve them or present them with alternatives that more attractive than being put on clinical hold…We know it can put shudders down investors’ spines when they see that. Especially for small companies.”

The comments come as Jefferies’ Michael Yee in Feb. 2022 detailed the sharp rise of FDA-imposed holds (RegenxBio even sued over a hold) following a decade of relatively little movement. The primary cause of the spike, Yee writes, is the vast increase in gene and cell therapy trials being conducted in recent years.

With more than 1,300 active INDs for gene therapies and over 1,200 active INDs for cell therapies, Marks and company have their work cut out for them, especially considering their past hiring woes, senior leader departures and backlog after the pandemic.

“There are some real challenges right now,” he said at the Food Drug and Law Institutes’ annual meeting while noting (see below) how the space is at a “critical juncture.”

“As capital has dried up, it’s become clear it’s not just an easy, quick win to get something across the finish line,” Marks said. “We’ve seen people really daunted by the manufacturing challenges, the clinical development timelines. And something that’s just a fact is that there are different global regulatory regulations that have made it challenging in this rare disease space.”

As far as commercial viability for gene therapies, which he also discussed Wednesday at the annual American Society of Gene and Cell Therapy meeting, he noted the optimal range for production is about 100 to 200 doses per year. “That’s where a lot of companies feel when they do the net present value calculation, the asset is actually worthwhile,” he said.

Sankalp Sethi

Sankalp Sethi, cell and gene therapy practice lead at the consulting firm ZS, told Endpoints News that he thinks cell and gene therapies will show whether they can be sustainable over the next three to five years.

“There’s work to be done in establishing that value proposition of these therapies as we get into chronic areas beyond oncology and beyond rare diseases,” Sethi said.

The entire industry is also going to keep close tabs on the type of evidence that is going to warrant some of the high price tags — CSL is marketing its hemophilia B gene therapy Hemgenix at a list price of $3.5 million — and, in many cases, are necessary to make these therapies commercially viable given the high cost of manufacturing, ZS manager Curt Kugel told Endpoints.

Marks also noted the “little progress in commercial viability over the past five years,” but the agency has its sights set on the future and is now trying to better define the use of accelerated approval for rare disease gene therapies, he said, adding, “they’re going to have to become part of what we do.”

“We actually will have to follow the science,” he said, regarding which accelerated approvals might be allowed for these therapies. “We won’t be able to have a magic wand and say, ‘poof,’ everything gets an accelerated approval.”

Marks again mentioned his plan to drive the next Operation Warp Speed for rare diseases pilot — a Federal Register notice seeking public comment is coming soon — that will allow for more real-time conversations between sponsors and FDA.

Operation Warp Speed for rare diseases: CBER leader says pilot is coming soon

“We’re really trying to lean in here because we think it could make a difference for a lot of people,” Marks said.