To date, 66 RMAT (Regenerative Medicine Advanced Therapy) designations have been publicly announced. However, the FDA states it has received 194 requests and issued 76, which means that a handful are not yet public knowledge.
Sponsors of cell and gene therapies are eligible to obtain an RMAT designation from the U.S. FDA if their product is intended to treat serious or life-threatening diseases and there is preliminary clinical evidence that it can address unmet medical needs.
Thus far, AlloVir is the only company to receive three RMATs, while six companies (Abeona Therapeutics, Allogene Therapeutics, Athersys, CARsgen Therapeutics, Rocket Pharmaceuticals, and CRISPR Therapeutics) have received two RMAT designations from the U.S. FDA.
RMAT Designations by the U.S. FDA
In this article:
List of RMAT Designations
Below is a comprehensive list of publicly announced RMAT designations:
- Abeona Therapeutics – EB-101 for treatment of Recessive RDEB (01/29/18)
- Abeona Therapeutics – ABO-102 for treatment of Sanfilippo Syndrome Type A (MPS IIIA) (04/23/18)
- Adaptimmune Therapeutics – ADP-A2M4 for the treatment of Synovial Sarcoma (12/03/19)
- Allogene Therapeutics – ALLO-715 for relapsed/refractory multiple myeloma (04/21/21)
- Allogene Therapeutics – ALLO-501A in relapsed/refractory LBCL (06/08/22)
- Allovir – Posoleucel (Viralym-M, ALVR105) for treatment of BK Virus-associated Hemorrhagic Cystitis after HSC Transplant (06/11/19)
- Allovir – Posoleucel (Viralym-M, ALVR105) for the treatment of adenovirus (AdV) infections post-allogeneic stem cell transplantation (01/05/22)
- Allovir – Posoleucel (Viralym-M, ALVR105) for prevention of clinically significant infections and disease from six devastating viruses that commonly impactpatients following allogeneic hematopoietic cell transplant (04/20/22)
- Angiocrine Bioscience – AB205 for the treatment of organ vascular niche injuries for the prevention of severe toxicities in lymphoma patients (11/11/20)
- Asterias Biotherapeutics (Acquired by Lineage Cell Therapeutics) – AST-OPC1 for treatment of Spinal Cord Injury (SCI) (10/02/17)
- Athersys – MultiStem for Ischemic Stroke (10/05/17)
- Athersys – MultiStem for Acute Respiratory Distress Syndrome (ARDS) (09/23/20)
- Audentes Therapeutics – AT132 for IX-linked Myotubular Myopathy (XLMTM) (08/21/18)
- Autolus Therapeutics – Obecabatagene autoleucel (obe-cel), a CD19-directed autologous CAR-T therapy that is being investigated in an ongoing FELIX Phase 2 study of adult relapsed / refractory B-Acute Lymphocytic Leukemia (04/25/22).
- AxoGen, Inc. – Avance® Nerve Graft for Peripheral Nerve Repair (10/29/18)
- BioMarin Pharmaceutical – Valoctocogene roxaparvovec, a gene therapy for adults with severe hemophilia A (03/08/21)
- bluebird bio – LentiGlobin for Severe Sickle Cell Disease (10/01/17)
- Bristol-Myers Squibb – Liso-cel, an autologous anti-CD19 CAR-T cell therapy for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) (12/18/19)
- Caladrius Biosciences – CLBS14 (CD34+ cell therapy program) for Refractory Angina (10/01/17)
- Capricor Therapeutics – CAP-1002 for Duchenne Muscular Dystrophy (02/05/18)
- CARsgen Therapeutics – CT053 (CAR-T therapy) for Relapsed or Refractory Multiple Myeloma (10/28/19)
- CARsgen Therapeutics– CT041 for patients wih advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) with Claudin18.2-positive tumor (01/10/22)
- Cellerant Therapeutics – Romyelocel-L for Prevention of Infections During Neutropenia (07/02/2018)
- Cellular Biomedicine Group Inc (CBMG) – C-CAR039 for use in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (01/12/22).
- Cook Myosite – Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR), for treatment of stress urinary incontinence (SUI) following surgical treatment (12/17/20)
- CRISPR Therapeutics – CTX001™ for Severe Hemoglobinopathies (05/11/20)
- CRISPR Therapeutics – CTX110™, an allogeneic CAR-T cell therapy targeting CD19+ B-cell malignancies (11/22/2021)
- Direct Biologics – Exoflo, an extracellular vesicle (EV) drug product, to treat Covid-19-linked acute respiratory distress syndrome (04/12/22)
- Enzyvant – Rethymic (originally RVT-802) for DiGeorge Syndrome (04/17/17)
- ExCellThera – ECT-0012 for Hematologic Malignancies (04/23/19)
- Fate Therapeutics – FT516, a gene-edited iPSC-derived NK cell therapy, for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) (12/13/21)
- Fibrocell – FCX-007 for Recessive Dystrophic Epidermolysis Bullosa (05/29/19)
- Fortress Biotech (Subsidiary Cellvation Inc.) – EVA101 for Traumatic Brain Injury (11/08/17)
- Helixmith Co., Ltd. (Previously ViroMed) – VM-202 for Diabetic Peripheral Neuropathy (05/30/18)
- Humacyte – Humacyl for Vascular Access for Hemodialysis (03/20/17)
- Immunicum AB – Ilixadencel, activated allogeneic dendritic cells that act as an immune primer for the treatment of metastatic Renal Cell Carcinoma (05/06/20)
- Iovance – Lifileucel for Advanced Melanoma (10/11/18)
- jCyte – jCell for Retinitis Pigmentosa (05/02/17)
- Juno Therapeutics (with Celgene Corp) – JCAR017 for Lymphoma (large B cell NHL) (11/01/17)
- Kiadis Pharma – ATIR101 for Leukemia (9/20/17)
- Krystal Biotech – KB103 for Wound Closure for RDEB Patients (06/24/19)
- Magenta Therapeutics – MGTA-456 for Multiple Inherited Metabolic Disorders, including Cerebral Adrenoleukodystrophy (09/04/19)
- Mallinckrodt Pharmaceuticals – Stratagraft for Thermal Burns (07/18/17)
- Medeor Therapeutics – MDR-101 to prevent kidney transplant rejection without chronic use of immunosuppressive drugs (09/22/20)
- Mesoblast – MPC-150-IM for Heart Failure (12/21/17)
- MiMedx Group – AmnioFix® Injectable for Knee Osteoarthritis (03/09/18)
- Mustang Bio (St. Judes)– MB-107 for X-linked Severe Combined Immunodeficiency (“Bubble Boy” Disease) (08/22/19)
- Nightstar Therapeutics – NSR-REP1 for Choroideremia (progressive vision loss) (06/14/18)
- Novartis – Kymriah® for patients with relapsed or refractory (r/r) follicular lymphoma (04/22/20)
- Ocugen – NeoCart® for the repair of full-thickness lesions of the knee cartilage in adults (05/24/22)
- Orca Bio – Orca-T, an experimental allogeneic cell therapy for patients with blood cancers who are eligible for a hematopoietic stem cell transplant (10/15/20).
- Orchard Therapeutics – OTL-103 for Wiskott-Aldrich Syndrome (07/29/19)
- Organogenesis – ReNu® for Knee Osteoarthritis (01/11/21)
- PolarityTE – SkinTE® for a chronic cutaneous ulcers and skin conditions (05/13/2022)
- Poseida Therapeutics – P-BCMA-101 for Relapsed/Refractory Multiple Myeloma (11/05/18)
- ProKidney – REACT® (Renal Autologous Cell Therapy) for slowing the progression of Chronic Kidney Disease (CKD) and improving kidney function (01/18/22)
- Rocket Pharmaceuticals – RP-L102 for Fanconi Anemia (11/27/18)
- Rocket Pharmaceuticals – RP-L201, an investigational gene therapy for Leukocyte Adhesion Deficiency-I (LAD-I) (03/09/21)
- SanBio – SB623 for Chronic motor deficits secondary to TBI (09/20/19)
- Sangamo Therapeutics – SB-525 for Severe Hemophilia A (07/05/19)
- Takeda – Alofisel for the treatment of perianal fistulas (02/10/21)
- Talaris – FCR-001 for Preventing Renal Transplantation Rejection (04/18/19)
- Tessa Therapeutics – CD30-directed autologous CAR-T cell therapy for relapsed or refractory CD30-positive Hodgkin lymphoma (02/27/20)
- TissueTech, Inc. – Cryopreserved human umbilical cord product, TTAX02 (04/16/20)
- Vericel Corporation – Ixmyelocel-T for Dilated Cardiomyopathy (05/10/17)
- Voyager Therapeutics – VY-AADC for Advanced Parkinson’s disease (06/21/18)
Total RMATs Received and Awarded by FDA
To date, the U.S. FDA has received at least 194 requests for RMAT designations and granted 76.
The table below presents the cumulative number of RMAT requests that the FDA has received by year.
*Source: U.S. FDA
What is an RMAT?
RMAT is an acronym that stands for “Regenerative Medicine Advanced Therapy.” The designation was introduced in December 2016 as part of the 21st Century Cures Act.
An RMAT submission request must be made in conjunction with an Investigational New Drug application (IND), either concurrently or as an amendment to an existing IND.
Products eligible for an RMAT designation include:
- Cell therapies
- Gene therapies
- Therapeutic tissue engineering products
- Human cell and tissue products
- Combination products using such therapies or products
By definition, an RMAT is an award from the U.S. FDA that allows for faster, more streamlined approvals of regenerative medicine products within the United States, such as cell and gene therapies, tissue engineering products, and combination products. RMAT designations make innovative products eligible for quicker development and review of a marketing application.
An RMAT designation is similar to the breakthrough therapy designation that is available to drugs.
Benefits of an RMAT include increased opportunities to meet with FDA officials, as well as early meetings to discuss potential surrogate or intermediate endpoints.
21st Century Cures Act
The 21st Century Cures Act was passed by the 114th U.S. Congress in December 2016. The act authorize $6.3 billion in funding, most of which is allocated for the National Institutes of Health (NIH).
The bill, passed by both houses of Congress and signed into law by President Obama, puts the U.S. on the same playing field as other countries that support accelerated of innovative medicines. Other regions that have accelerated pathways include Japan, South Korea, and the EU. The bill encourages late-stage development in regenerative medicine, recognizing the field’s potential to address severe unmet medical needs.
Congress included several provisions related to cell and gene therapies in the 21st Century Cures Act, the most important of which is the RMAT designation.
RMAT Reviews by The FDA
For more detail, the following is from the U.S. FDA:
As described in Section 3033 of the 21st Century Cures Act, a drug is eligible for regenerative medicine advanced therapy (RMAT) designation if:
- The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
- The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
- Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.
Who do you expect to appear next on this RMAT list? Share your guesses in the comments below.