Regenerative Medicine Advanced Therapy (RMAT) is a designation given by the Food and Drug Administration to drug candidates intended to treat serious or life-threatening conditions under the 21st Century Cures Act. A RMAT designation allows for accelerated approval based surrogate or intermediate endpoints.

RMAT goes beyond breakthrough therapy features by allowing for accelerated approval of drugs based on surrogate endpoints. A surrogate endpoint is a biomarker that substitutes for a direct endpoint, such as clinical benefit.

Legal background Section 3033 of the 21st Century Cures Act introduces section 506(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) that allows for the designation of certain therapies as a 'regenerative medicine advanced therapy' (RMAT) ().

Qualifying criteria In order to qualify for RMAT status, a treatment must

meet the definition of a regenerative medicine therapy, intend to treat, modify, reverse or cure a serious condition, and be supported by preliminary clinical evidence that indicates the RMAT candidate can address the clinical need.

A regenerative medicine therapy is defined in section 506(g)(8) of the FD&C Act to include cell therapies, therapeutic tissue engineering, human cell and tissue products. Under the FDA's interpretation, gene therapies and genetically modified cells that have a lasting effect, such as CAR-T antitumor therapies, may also qualify as regenerative medicine therapies.

Effect A RMAT designation includes all benefits of the Fast Track and breakthrough therapy designations. In addition, it opens up early interactions between the FDA and sponsors to facilitate accelerated approval. In this context, accelerated approval means approval based on

previously agreed-upon surrogate or intermediate endpoints, or data from a limited but meaningful number of sites.

The ability to use 'Real World Evidence' (RWE), i.e. post-market evidence of safety and effectiveness, is particularly useful in the context of orphan diseases, where recruiting a sufficiently large cohort for pre-marketing clinical trials may not be feasible. RWE may include data from patient registries, clinical records and case studies.

Where a RMAT's sponsor fails to comply with the requirements for accelerated approval, the RMAT designation and the benefits conferred by it can be withdrawn ().

Examples

+List of pharmaceuticals designated as RMATsNameDesigneeTypeBiological targetTherapeutic indicationRPESC-RPE-4WLuxa Biotechnologyautologous stem cellretinal pigment epitheliumDry age-related macular degeneration and geographic atrophyED-101Abeona Therapeuticscell therapyCollagen, type VII, alpha 1Recessive dystrophic epidermolysis bullosaABO-102Abeona Therapeuticsgene therapySGSHMucopolysaccharidosis Type III (Sanfilippo syndrome)ADP-A2M4Adaptimmune TherapeuticsSPEAR T-cellsMAGEA4Synovial sarcomaALLO-715Allogene Therapeuticsallogeneic CAR-TB-cell maturation antigenRefractory/relapsed multiple myelomaALVR-105 Viralym-MAllovirallogeneic CAR-TBK virus, CMV, adenoviridae, Epstein–Barr virus, human herpesvirus 6, JC virus (human polyomavirus 2)BK virus associated hemorrhagic cystitis after hematopoietic stem cell transplantationAB205Angiocrine Bioscienceallogeneic cord endothelial cellsSevere regimen-related toxicities from conditioning chemotherapy prior to hematopoietic stem cell transplantation in patients with lymphomasAST-OPC1Asterias Biotherapeuticsallogeneic oligodendrocyte progenitor cellsSpinal cord injuriesAT132Audentes Therapeuticsgene therapyMyotubularin 1X-linked myotubular myopathyValoctocogene roxaparvovec (Roctavian,

Valrox)BioMarin Pharmaceuticalgene therapyF8Haemophilia ABetibeglogene autotemcel (Lentiglobin)bluebird biogene therapyHemoglobin subunit betaSickle cell diseaseLisocabtagene maraleucel (Breyanzi)Bristol Myers Squibbautologous CAR-TCD19Diffuse large B-cell lymphomaCLBS14 (Ologo)Caladrius Biosciencesautologous cell therapyCD34Refractory anginaCAP-1002Capricor Therapeuticsallogeneic cell therapyDuchenne muscular dystrophyCT053CARsgen Therapeuticsautologous CAR-TB-cell maturation antigenRefractory or relapsed multiple myelomaDescartes-08Cartesian Therapeutics, Inc.autologous RNA CAR-TB-cell maturation antigenGeneralized myasthenia gravisRomyelocel-LCellerant Therapeuticsallogeneic cell therapySerious bacterial and fungal infections during induction chemotherapy in acute myeloid leukemiaCTX001CRISPR Therapeutics Vertex Pharmaceuticalsgene therapyFetal hemoglobinSickle cell disease Transfusion-dependent beta thalassemiaRVT-802Enzyvantallogeneic cell therapyThymus tissueCongenital athymia in DiGeorge syndromeECT-001ExCellTheraallogeneic cell therapyHematologic malignanciesFCX-007 (dabocemagene autoficel)Fibrocell Castle Creek Biosciencesgene therapyCollagen, type VII, alpha 1Recessive dystrophic epidermolysis bullosaIlixadencelImmunicum ABallogeneic cell therapyRenal cell carcinomaLifileucelIovance Biotherapeuticsautologous cell therapyMetastatic melanoma that progresses after an anti-PD-1 treatmentMGTA-456Magenta Therapeuticsallogeneic cell therapyCD34Promoting hematopoietic stem cell transplant engraftment in Hurler syndrome, metachromatic leukodystrophy and Krabbe diseaseMDR-101Medeor Therapeuticsallogeneic cell therapyCD34, CD3Prevention of kidney transplant rejectionMB-107Mustang Bio St. Jude Children's Research Hospitalgene therapyCommon gamma chainX-linked severe combined immunodeficiencyRP-L102Rocket Pharmaceuticals Inc.gene therapyFANCAFanconi anemiaVY-AADCVoyager Therapeuticsgene therapyAromatic L-amino acid decarboxylaseParkinson's diseaseRP-L201Rocket Pharmaceuticals Inc.gene therapy using autologous CD34+ enriched cellsIntegrin beta 2Leukocyte adhesion deficiency Type IOTL-103Orchard Therapeuticsgene therapy using autologous cellsWASpWiskott–Aldrich syndrome

Statistics In 2020, the FDA received 34 requests for RMAT status, of which 12 (35.3%) were granted. RMAT designated drugs include the novel CAR-T therapy Kymriah and betibeglogene autotemcel for beta thalassemia. As of 31 March 2021, 62 requests for RMAT status have been granted.

More than half of the RMAT applications received by March 2019 involved autologous or allogeneic cell therapy products, including CAR-T therapies.

See also

Breakthrough therapy Advanced Therapy Medicinal Product (European Medicines Agency equivalent) Sakigake (Japanese equivalent) Orphan drug

References