Authored by: Mo Heidaran
In the 21st Century Cures Act Title III, Sections 3033-3036, Congress created a new program for designation of Regenerative Medicine Advanced Therapy (RMAT). In November of 2017, FDA published a draft guidance entitled “Expedited programs for Regenerative Medicine Therapies for Serious and Life Threatening conditions” to further clarify the product types covered by this new program and the major requirements for RMAT designation (Section IIIc).
The 2017 draft guidance clarified that the program covers a therapy if:
- The therapy meets the definition of regenerative medicine therapy;
- The Therapy is intended to treat, modify, reverse, or cure a serious condition; and
- Preliminary clinical evidence indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such condition.
In section II of the guidance, FDA further defines the types of advanced therapies which are defined in section 506(g)(8) of the FD&C Act, as including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, except for those regulated solely under section 361 of the Public Health Service Act (PHS Act) and 21 CFR Part 1271. As FDA interprets section 506(g) of the FD&C Act, gene therapies, including genetically modified cells, that lead to a durable modification of cells or tissues may meet the definition of a regenerative medicine therapy. Additionally, a combination product (biologic-device, biologic-drug, or biologic-device-drug) can be eligible for RMAT designation when the biological product component provides the greatest contribution to the overall intended therapeutic effects of the combination product (i.e., the primary mode of action in the combination product is conveyed by the biological product component).
The benefits of RMAT designation are very similar to breakthrough (BT) designation and include more opportunities to meet with FDA throughout the product development lifecycle and the involvement of senior managers and more-experienced review staff. While RMAT is not a guarantee for Accelerated Approval or Priority Review, those programs may also be applicable.
According to the most recent update provided by Director of CBER/OTAT (https://aabb.confex.com/aabb/ICBS18/mediafile/Handout/Paper3123/Regenerative%20Medicine%20Advanced%20Therapy%20%28RMAT%29.pdf), sponsors can request RMAT designation for an active IND (not on clinical hold) or at the time of submitting a new IND and the request should include a) how a drug meets the definition of regenerative medicine, b) how the drug meets the criterion for treating, reversing or curing a serious and life threatening disease or condition, and c) preliminary clinical evidence indicating the drug has potential to address unmet medical need. FDA has 60 calendar days to determine if designation requirements are met. If the designation is not granted by FDA, they will provide a reason for denial.
The RMAT designation request status as of June 12, 2018, includes 33 denials, 22 granted and 6 pending. By product type, 13 were considered cell therapy products (Autologous), 28 were considered cell therapy products (Allogeneic), 11 were considered to be gene therapy, and 9 belong to other categories. The RMAT requests covered products which were primarily in Phases II and III (16 Phase 1, 27 Phase 2 and 18 Phase 3). Major reasons for denial were cited as a) inactive IND; b) no preliminary clinical data included in the submission; c) CMC reason (Different Product) and d) Insufficient preliminary clinical evidence.
PAREXEL can help our clients craft strategies for and set the content of RMAT designation packages to help avoid major bottlenecks cited by the agency.