by Annegret Wiedemann

FDA recently introduced the new Regenerative Medicine Advanced Therapy (RMAT) Designation in the framework of the 21st Century Cures Act. This new FDA pathway enables companies developing cell- and tissue-based therapies, tissue-engineering products, and combination treatments to have earlier and more frequently interactions with the agency and benefit from proactive collaboration with FDA.

Regenerative medicinal products hold great promise in addressing serious unmet medical needs. To help foster their development and approval FDA introduced the new Regenerative Medicine Advanced Therapy (RMAT) Designation in the framework of the 21st Century Cures Act. This new FDA pathway enables companies developing cell- and tissue-based therapies, tissue-engineering products, and combination treatments to have earlier and more frequently interactions with the agency and benefit from proactive and collaborative involvement by senior FDA managers and experienced review and regulatory health project management staff. Moreover, RMAT-designated products may be eligible for priority review, accelerated approval, and the FDA may conduct a rolling review, reviewing portions of a marketing application before the complete application is submitted to speed up the approval. To qualify for RMAT the drug must be intended to treat a serious or life-threatening disease and the company has to present preliminary clinical evidence (generally derived from phase 1 or 2 trials) indicating that the drug has the potential to address unmet medical needs for such disease or condition. Since the programs introduction in March, the FDA received 17 applications for the RMAT designation so far, four of which have been granted already, which demonstrates that FDA is embracing the spirit of the Cures provisions. The four products receiving RMAT designation are:

HUMACYL from Humacyte, which uses smooth muscle cells from the aortic tissue of heart transplant donors to create a scaffold of extracellular matrix proteins. The product is intended to decrease vascular access complications in hemodialysis patients that in turn may result in more favorable outcomes in case of morbidity and mortality.

from Humacyte, which uses smooth muscle cells from the aortic tissue of heart transplant donors to create a scaffold of extracellular matrix proteins. The product is intended to decrease vascular access complications in hemodialysis patients that in turn may result in more favorable outcomes in case of morbidity and mortality. Ixmyelocel-T from Vericel is an expanded, multicellular therapy produced from a patient's own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Ixmyelocel is intended for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy.

from Vericel is an expanded, multicellular therapy produced from a patient's own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Ixmyelocel is intended for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy. jCell from j-cyte, containing human retinal progenitor cells (hRPCs), which release neurotrophic factors that may rescue diseased retinal cells, as well as possibly integrate as new cells into the retina, intended for the treatment of retinitis pigmentosa.

from j-cyte, containing human retinal progenitor cells (hRPCs), which release neurotrophic factors that may rescue diseased retinal cells, as well as possibly integrate as new cells into the retina, intended for the treatment of retinitis pigmentosa. RVT-802 from Enzyvant intended for the treatment of DiGeorge Syndrome which uses a proprietary process to harvest, culture, and apply allogeneic thymic tissue.

The request for RMAT designation has to be made either concurrently with submission of an Investigational New Drug application (IND) or as an amendment to an existing IND.

To recap, RMAT designation allows the sponsor to profit by breakthrough and priority review benefits as well as by fast track’s rolling review. In addition, with RMAT designation, the sponsor will have the opportunity for accelerated approval on the basis of a validated surrogate endpoint and benefit from reduced phase 4 requirements if the product is approved.

RMAT designation is an exciting opportunity to validate a company’s efforts and to attract investors. But still there remain challenges (e.g. the serious condition provision) for the applicant to address especially as this program is new to both regulators and applicants.

Biopharma excellence has the specialized knowledge, information, and resources needed to guide interested providers carefully on their way to RMAT. Do not hesitate to contact us for more information.