Interview with Peter Marks of FDA

Peter Marks received his graduate and medical degrees from New York University. Following this, he completed an Internal Medicine residency and Hematology/Medical Oncology fellowship at Brigham and Women’s Hospital in Boston, where he subsequently joined the attending staff as a clinician-scientist and eventually served as Clinical Director of Hematology. He then moved on to work for several years in the pharmaceutical industry prior to returning to academic medicine at Yale University where he served as Chief Clinical Officer of Smilow Cancer Hospital. Read his full bio.

Interview with Dr. Peter Marks, Director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER)

Q: The CBER’s Regenerative Medicine Advanced Therapy Designation program has been very successful, with about 100 requests for designation in the two years of its existence. Can you please tell us about the program and how it was put together?

A: The Regenerative Medicine Advanced Therapy (RMAT) Designation program came into being as part of the 21st Century Cures Act that was signed into law on December 13, 2016. It was conceived as a program to address the unique development needs of cell, tissue and gene therapies. The requirements and benefits of the program are much the same as for breakthrough therapy designation (access to all expedited programs, addition meetings and senior management involvement), with two key differences. First, the standard for the level of evidence required to obtain RMAT designation is not as stringent as for breakthrough therapy designation, relying on the potential to address unmet medical needs, rather than demonstration of an improvement over an existing standard of care. Second, product receiving an accelerated approval through RMAT designation are eligible to use an expanded range of options to fulfill the post-approval requirement for additional evidence to obtain full approval, including submission of larger datasets and use of real-world evidence, when appropriate.

Q: Many of the investigational agents in clinical trials are for rare diseases. How CBER takes into consideration what matters most for patients in deciding on the most relevant endpoints?

A: CBER has joined in with the other medical product centers at FDA embracing patient focused drug development. We engage with patients, patient advocacy groups, and sponsors in a variety of settings. A recent example of this approach is illustrated by the endpoint used for the approval of voretigene, the directly-administered gene therapy for retinal dystrophy caused by RPE65 mutations. It this instance, industry collaborated with FDA to develop a novel endpoint, the multiluminance mobility test – a maze with obstacles navigated by patients under different light levels – that captured what mattered most to patients: the ability to navigate on their own in lower light levels.

Q: What are the challenges in regulating the manufacturing and quality attributes of the emerging cellular and gene therapies?

A: Because it is still early in the days of process development for cellular and gene therapies, settling on what the critical quality attributes are for a given product can still be quite challenging. CBER is working with various partners to try to better define specific parameters for the various products and processes. In the meantime, we are very open to discussions with sponsors regarding their proposals for potential critical quality attributes that could be monitored as part of their processes.

Q: What types of therapies do you think will be considered for approval in the near future?

A: Though we can’t speak about specific products or provide any sort of a timeline, given the recent cellular and gene therapy approvals, it would be reasonable to predict that we may see additional chimeric antigen receptor T cells (CAR T cells) and other directly administered gene therapies coming to market in the not too distant future. The pace of progress in this area is clearly ramping up, with over 800 active investigational new drug applications on file for gene therapies at the agency.