Marks eyes gene therapy development pilot, sees uptick in successful RMAT requests

Peter Marks, director of Center for Biologics Evaluation and Research (CBER) at the US Food and Drug Administration (FDA), attributes an increase in the amount of regenerative medicine advanced therapy (RMAT) requests approved for cell and gene therapies to sponsors “getting the hang” of the agency’s expectations for designation requests.
 
Marks spoke at the California Separation Science Society’s (CASSS) meeting on 8 June on cell and gene therapies. The meeting was held both in-person in Arlington, VA and virtually.
 
Marks also expressed interest in starting a gene therapy pilot program where sponsors would get real-time feedback from FDA reviewers on their development programs. The pilot would test which approaches work best and which do not in developing these products. This would help to avoid setting regulatory policies for approaches that are impractical.
 
Slight uptick in RMAT acceptance
 
The RMAT program was established by the 21^st Century Cures Act in 2016 to expedite the development and approval of cell and gene theories products. To quality for RMAT designation, products must be intended to treat serious or life-threatening diseases or conditions, and preliminary evidence must indicate the treatment’s potential for addressing unmet medical needs. FDA will reply to designation requests within 60 days. Designated products are also eligible for priority review and accelerated approval.
 
As of 31 March 2022, CBER has received more than 180 requests for designation, and has granted 38% of these requests and denied 56% of them. A small number of requests have been withdrawn or are currently pending.
 
Marks said that “one of the nice trends that we’re seeing is a slight uptick in the number of requests that we are able to grant from the number of designations submitted. People seem to be getting more of a hang of what we’re looking for, hopefully that trend will continue.”
 
He added that many of these designations are for cell therapies while “some” of these are for gene therapies. Roughly half of the RMATs are for rare diseases, and a number of these are for rare diseases with an orphan product designation.
 
Marks said the reason for the denials has “shifted over time” when asked to address the reasons for the rejections at the meeting. The most common reason is that the data generated from the trials does not show a clear treatment difference between the patients that were treated with the therapy and those that were not.
 
“The most common reason for denial is not because the product is not going to treat the serious illness. The problem is that the data generated is often times very hard to see that there is a clear difference in those few patients who have been treated than those who were not.”
 
Marks interested in gene therapy pilot program
 
Marks also expressed interest in establishing a gene therapy product development program in which FDA would work with sponsors that are developing these therapies to provide “real time feedback” on their programs. He said this type of feedback and interaction would be similar to Operation Warp Speed, a federal initiative aimed at speeding the development and production of COVID-19 vaccines, therapeutics and diagnostics.
 
During a question-and-answer session at the end of the panel, Marks said that the pilot would aim to address capacity challenges at the agency and would shed some early light on what approaches work and what does not work before FDA implements regulatory processes.
 
“My rationale here for trying to do some pilots is that no we don’t have the resources right now to give the type of individual services that we would like to be able to do.” Yet, the pilot would “show Congress that ‘yes, we did this pilot and in X number of cases we were able to expedite the development of this product by X percent.’” Through this pilot, he added FDA would be able to “get Congress excited about what is possible to have if you are able to have these types of interactions.”
 
CASSS meeting