CBER Director Focuses on Flexibility to Advance Regenerative Medicines

Print 11 May 2017
Michael Mezher / Regulatory Affairs Professionals Society

Peter Marks, director of the US Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) on Thursday said his office is equipped to support the development of cutting edge treatments, such as cell and gene therapies.

Speaking at the Food and Drug Law Institute's annual conference, Marks said the 21st Century Cures Act added tools to FDA's regulatory arsenal, including the regenerative medicine advanced therapy (RMAT) designation to provide for more interactions with FDA and access to the agency's existing expedited approval programs will help guide the development of such products.

"The great part of this is this provision did not lower the safety and effectiveness standard … although we have tremendous flexibility, which we intend to use," Marks said.

"We don't stand on ceremony—forget about the old two randomized controlled trials—single arm, compelling studies are okay in this setting," Marks said, adding that trials of 10 or 20 patients for gene therapy trials for rare diseases may be "compelling enough" for approval, and that the agency could look to creative endpoints for such products.

Marks also said the agency is "very open to entertaining expanded access programs," where appropriate, though he said clinical trials remain the best way to access unapproved treatments.

So far, Marks said, the RMAT designation has been popular with industry, though he was unable to comment on how many requests the agency has received so far.

"Just as Dr. [Janet] Woodcock in [the Center for Drug Evaluation and Research] CDER was able to mobilize resources to put towards breakthrough because it was important, we will do what we need to," he said, referring to the greater than expected interest in the agency's breakthrough therapy designation.

Two companies, Humacyte and Enzyvant, have already announced they have received the RMAT designation, and Marks said the first request for the designation came on 14 December 2016, just one day after Cures was signed into law.

"It's amazing how much conversations with the agency can save developers in terms of time. Sometimes the conversation saves them much more time than would be saved by just having us be able to get through a review three months faster," Marks said.

Michael Werner, a life sciences partner at the law firm Holland & Knight, called the RMAT designation a "shot in the arm" for industry, and said it signaled the US' intention to keep pace with countries such as Japan and the UK, both of which have taken steps to promote advanced therapies in recent years.

However, Dan Kracov, co-chair of Arnold & Porter's life sciences and healthcare regulatory practice, said the conversation needs to move "beyond the RMAT designation," to focus on incentives to encourage precompetitive collaboration within industry and address the issue of cost and access for products such as gene therapies.

"In most cases, [gene] therapies are going to cost $750,000, a million dollars, for one patient. That is an area where we have a very significant problem that FDA can't solve," Kracov said.

So far, industry has struggled with commercializing the two gene therapies that have received approval in Europe, UniQure's Glybera and GlaxoSmithKline's Strimvelis, which are among the most expensive medicines in the world.

UniQure announced in April that it would not be renewing its marketing authorization for Glybera, which costs $1 million per treatment, as a result of low demand. And, last week MIT Technology Review reported that Strimvelis—which costs around $650,000 and comes with a money back guarantee—has only been used to treat a single patient since it was approved in May 2016.

Despite these challenges, a number of gene therapies are currently in development, and the US could see its first gene therapy approval as early as this year. In February, Spark Therapeutics announced it was "in the final stages" of its rolling biologics license application (BLA) for its gene therapy candidate SPK-RPE65 to treat mediated inherited retinal disease.

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