FDA Looks to Advance Regenerative Medicine

The Center for Biologics Evaluation and Research (CBER) is gearing up to facilitate the development and approval of regenerative medicine advanced therapies (RMAT) as defined and advanced by the 21^st Century Cures Act. The legislation calls for FDA to set standards and to issue guidance on developing these treatments, which includes certain cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products intended to treat serious or life-threatening diseases or conditions. Genetically-modified cellular therapies, such as chimeric antigen receptor T-cells (CAR-T cells), and human tissues grown on scaffolds for subsequent use fall under the RMAT umbrella.

An important Cures provision establishes the RMAT designation process to identify experimental products that warrant additional attention from FDA. Sponsors can seek the RMAT designation, which offers early interactions with FDA staff, similar to the assistance provided for breakthrough therapies. Priority review and accelerated approval also may be authorized based on preliminary clinical evidence that the therapy has potential to address unmet medical needs.

At least two biomedical firms have acknowledged receiving a RMAT designation, and others are under consideration by CBER’s Office of Tissues and Advanced Therapies , which oversees this emerging field.

The Cures legislation is important in authorizing FDA to help streamline the development of regenerative medicines, commented CBER director Peter Marks at the annual meeting of the Food and Drug Law Institute (FDLI) in early May. FDA officials applaud the new policy for providing the agency with considerable flexibility in evaluating these cutting-edge products, while maintaining regulatory oversight of the field. Marks noted that FDA may not require two randomized controlled trials for testing RMAT therapies, and likely will decide that very small, single-arm studies are enough to support approval.

Attorney Michael Werner, partner at Holland & Knight, reported at the FDLI meeting that hundreds of clinical trials are underway in the “regenerative medicine space,” this activity increasing notably since enactment of the Cures legislation “acknowledged the potential of the field.” The new law established a more predictable regulatory process for these therapies, Werner commented, while maintaining high FDA standards for approval. He and others expect FDA to approve the first CAR-T therapies this year.

A major challenge will be providing reimbursement for future cutting-edge therapies that may cost up to $1 million per patient, pointed out Dan Kracov, partner at Arnold & Porter. The right incentives and payment policies will be needed to allow access to new gene therapies, he explained, noting interest in insurance pools and annuity programs to address these issues.

Marks said that FDA expects to accept a variety of endpoints for RMAT clinical trials, and that registries may be helpful in confirming the effect of orthopedic products for larger numbers of patients. The Cures legislation also requires FDA to develop guidance on developing devices for delivery of regenerative therapies. CBER is working with organizations and partnerships to establish standards for defining and characterizing these products and for conducting assays and dealing with environmental concerns. A main issue in producing cellular therapies is ensuring consistency in critical quality attributes for identify and purity.