To date, 47 RMAT (Regenerative Medicine Advanced Therapy) designations have been publicly announced. However, the FDA states it has received 149 requests and issued 55.
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.
The most recent addition to this list was Orca Bio for its experimental cell therapy, Orca-T. Orca-T is a formulation of hematopoietic stem cells and T cells provided to cancer patients who are eligible for a hematopoietic stem cell transplant (HSCT). Thus far, only two companies (Abeona Therapeutics and Athersys) 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 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)
- Allovir – Viralym-M (ALVR105) for treatment of BK Virus-associated Hemorrhagic Cystitis after HSC Transplant (06/11/19)
- Asterias Biotherapeutics – 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) (09/23/2020)
- Audentes Therapeutics – AT132 for IX-linked Myotubular Myopathy (XLMTM) (08/21/18)
- AxoGen, Inc. – Avance® Nerve Graft for Peripheral Nerve Repair (10/29/18)
- 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)
- Cellerant Therapeutics – Romyelocel-L for Prevention of Infections During Neutropenia (07/02/2018)
- Cellvation Inc. (Fortress Biotech Co.) – EVA101 for Traumatic Brain Injury (11/08/17)
- CRISPR Therapeutics and Vertex Pharmaceuticals – CTX001™ for Severe Hemoglobinopathies (05/11/20)
- Enzyvant – RVT-802 for DiGeorge Syndrome (04/17/17)
- ExCellThera – ECT-0012 for Hematologic Malignancies (04/23/19)
- Fibrocell – FCX-007 for Recessive Dystrophic Epidermolysis Bullosa (05/29/19)
- 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 used 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)
- 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)
- Poseida Therapeutics – P-BCMA-101 for Relapsed/Refractory Multiple Myeloma (11/05/18)
- Rocket Pharmaceuticals – RP-L102 for Fanconi Anemia (11/27/18)
- SanBio – SB623 for Chronic motor deficits secondary to TBI (09/20/19)
- Sangamo Therapeutics – SB-525 for Severe Hemophilia A (07/05/19)
- 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 149 requests for RMAT designations and granted 55 (37%). 47 of these have been publicly announced.
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.
Future RMAT Designations
There is also chatter within the industry that Tigenix will apply for an RMAT designation for Cx601, a local administration of expanded adipose-derived stem cells (eASCs).
Who do you expect to appear next on this RMAT list? Share your guesses in the comments below.