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 .
[1] A RMAT designation allows for accelerated approval based surrogate or intermediate
endpoints .
[2]
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.
[3]
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) (
21 U.S.C.
§ 356 ).
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.
[4]
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.
[4]
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.
[5] RWE may include data from patient registries, clinical records and case studies.
[6]
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to comply with the requirements for accelerated approval, the RMAT designation and the benefits conferred by it can be withdrawn (
21 CFR
601.43 ).
Examples
List of pharmaceuticals designated as RMATs
Name
Designee
Type
Biological target
Therapeutic indication
ED-101
[7]
Abeona Therapeutics
cell therapy
Collagen, type VII, alpha 1
Recessive dystrophic epidermolysis bullosa
ABO-102
[8]
Abeona Therapeutics
gene therapy
SGSH
Mucopolysaccharidosis Type III (Sanfilippo syndrome)
ADP-A2M4
[9]
Adaptimmune Therapeutics
SPEAR T-cells
MAGEA4
Synovial sarcoma
ALLO-715
[10]
Allogene Therapeutics
allogeneic
CAR-T
B-cell maturation antigen
Refractory/relapsed
multiple myeloma
ALVR-105
Viralym-M
[11]
Allovir
allogeneic
CAR-T
BK virus ,
CMV ,
adenoviridae ,
Epstein–Barr virus ,
human herpesvirus 6 ,
JC virus (human polyomavirus 2)
BK virus associated
hemorrhagic cystitis after
hematopoietic stem cell transplantation
AB205
[12]
Angiocrine Bioscience
allogeneic
cord
endothelial cells
Severe regiment-related toxicities from
conditioning chemotherapy prior to
hematopoietic stem cell transplantation in patients with
lymphomas
AST-OPC1
[13]
Asterias Biotherapeutics
allogeneic
oligodendrocyte progenitor cells
Spinal cord injuries
AT132
[14]
Audentes Therapeutics
gene therapy
Myotubularin 1
X-linked myotubular myopathy
Valoctocogene roxaparvovec
(Roctavian,
Valrox)
BioMarin Pharmaceutical
gene therapy
F8
Haemophilia A
Betibeglogene autotemcel
(Lentiglobin)
[15]
bluebird bio
gene therapy
Hemoglobin subunit beta
Sickle cell disease
Lisocabtagene maraleucel
(Breyanzi)
Bristol Myers Squibb
autologous
CAR-T
CD19
Diffuse large B-cell lymphoma
CLBS14
(Ologo)
[16]
Caladrius Biosciences
autologous
cell therapy
CD34
Refractory angina
CAP-1002
[17]
Capricor Therapeutics
allogeneic
cell therapy
Duchenne muscular dystrophy
CT053
[18]
CARsgen Therapeutics
autologous
CAR-T
B-cell maturation antigen
Refractory or relapsed
multiple myeloma
Descartes-08
[19]
Cartesian Therapeutics, Inc.
autologous
RNA
CAR-T
B-cell maturation antigen
Generalized
myasthenia gravis
Romyelocel-L
[20]
Cellerant Therapeutics
allogeneic
cell therapy
Serious
bacterial and fungal infections during
induction chemotherapy in
acute myeloid leukemia
CTX001
[21]
CRISPR Therapeutics
Vertex Pharmaceuticals
gene therapy
Fetal hemoglobin
Sickle cell disease
Transfusion-dependent
beta thalassemia
RVT-802
[22]
Enzyvant
allogeneic
cell therapy
Thymus tissue
Congenital athymia in DiGeorge syndrome
ECT-001
[23]
ExCellThera
allogeneic
cell therapy
Hematologic malignancies
FCX-007 (dabocemagene autoficel)
[24]
Fibrocell
Castle Creek Biosciences
gene therapy
Collagen, type VII, alpha 1
Recessive dystrophic epidermolysis bullosa
Ilixadencel
[25]
Immunicum AB
allogeneic
cell therapy
Renal cell carcinoma
Lifileucel
[26]
Iovance Biotherapeutics
autologous
cell therapy
Metastatic melanoma that progresses after an
anti-PD-1 treatment
MGTA-456
[27]
Magenta Therapeutics
allogeneic
cell therapy
CD34
Promoting
hematopoietic stem cell transplant engraftment in
Hurler syndrome ,
metachromatic leukodystrophy and
Krabbe disease
MDR-101
[28]
Medeor Therapeutics
allogeneic
cell therapy
CD34 ,
CD3
Prevention of
kidney transplant
rejection
MB-107
[29]
Mustang Bio
St. Jude Children's Research Hospital
gene therapy
Common gamma chain
X-linked severe combined immunodeficiency
RP-L102
[30]
Rocket Pharmaceuticals Inc.
gene therapy
FANCA
Fanconi anemia
VY-AADC
[31]
Voyager Therapeutics
gene therapy
Aromatic L-amino acid decarboxylase
Parkinson's disease
RP-L201
[32]
Rocket Pharmaceuticals Inc.
gene therapy using
autologous
CD34+ enriched cells
Integrin beta 2
Leukocyte adhesion deficiency Type I
OTL-103
[33]
Orchard Therapeutics
gene therapy using
autologous cells
WASp
Wiskott–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 .
[34] As of 31 March 2021, 62 requests for RMAT status have been granted.
[35]
More than half of the RMAT applications received by March 2019 involved
autologous or
allogeneic
cell therapy products, including
CAR-T therapies.
[6]
See also
References
^
"Regenerative Medicine Advanced Therapy Designation" . Food and Drug Administration. Retrieved 25 June 2021 .
^ Vaggelas, Annegret; Seimetz, Diane (2019-05-01).
"Expediting Drug Development: FDA's New Regenerative Medicine Advanced Therapy Designation" . Therapeutic Innovation & Regulatory Science . 53 (3): 364–373.
doi :
10.1177/2168479018779373 .
ISSN
2168-4804 .
PMID
29895180 .
S2CID
48355647 .
^ Aronson, J K (2005).
"Biomarkers and surrogate endpoints" . British Journal of Clinical Pharmacology . 59 (5): 491–494.
doi :
10.1111/j.1365-2125.2005.02435.x .
PMC
1884846 .
PMID
15842546 .
^
a
b Food and Drug Administration (February 2019).
"Expedited Programs for Regenerative Medicine Therapies for Serious Conditions: Guidance for Industry" .
Food and Drug Administration . Retrieved 25 June 2021 .
^ Barlas, Stephen (March 2018).
"The 21st Century Cures Act: FDA Implementation One Year Later" . Pharmacy and Therapeutics . 43 (3): 149–179.
ISSN
1052-1372 .
PMC
5821241 .
PMID
29491696 .
^
a
b
"Regulatory intelligence: Update on regenerative medicine advanced therapies designations" . Endpoints News . Retrieved 2021-06-25 .
^ Abeona Therapeutics Inc. (2018-01-29).
"Abeona Receives FDA Regenerative Medicine Advanced Therapy Designation for EB-101 Gene Therapy in Epidermolysis Bullosa" . GlobeNewswire News Room (Press release). Retrieved 2021-07-01 .
^
"Abeona Announces FDA Grants RMAT Designation to ABO-102 Gene Therapy in MPS IIIA" . Abeona Therapeutics Inc . Retrieved 2021-07-01 .
^
"Regenerative Medicine Advanced Therapy Designation Granted to ADP-A2M4 for Synovial Sarcoma" . Journal of Oncology Navigation & Survivorship . 2019-12-11.
^
"FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma" . OncLive . Retrieved 2021-07-01 .
^
"AlloVir Secures Latest RMAT Designation for Viralym-M" . BioInformant . 2019-06-12. Retrieved 2021-07-01 . [
permanent dead link ]
^
"Angiocrine Bioscience Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to AB-205 (Universal E-CEL® Cell Therapy) to Treat Organ Vascular Niche Injuries for the Prevention of Severe Toxicities in Lymphoma Patients" . BioSpace . Retrieved 2021-07-01 .
^ Asterias Biotherapeutics (2017-10-02).
"Asterias Announces Two Significant Developments for Spinal Cord Injury Program" . GlobeNewswire News Room (Press release). Retrieved 2021-07-01 .
^ Audentes Therapeutics Inc.
"Audentes Announces Regenerative Medicine Advanced Therapy (RMAT) Designation Granted by the FDA to AT132 for the Treatment of X-Linked Myotubular Myopathy" . www.prnewswire.com (Press release). Retrieved 2021-07-01 .
^
"bluebird bio's LentiGlobin™ for Sickle Cell Disease Gene Therapy (bb1111) Granted Priority Medicines (PRIME) Designation by European Medicines Agency - bluebird bio, Inc" . investor.bluebirdbio.com . Retrieved 2021-07-01 .
^ Caladrius Biosciences Inc. (2019-08-07).
"Caladrius Biosciences and Cognate BioServices Establish Manufacturing Agreement for Phase 3 Confirmatory Pivotal Clinical Trial of CLBS14 in No-option Refractory Disabling Angina" . GlobeNewswire News Room (Press release). Retrieved 2021-07-01 .
^ Capricor Therapeutics Inc. (2019-09-24).
"Capricor Therapeutics to Meet with FDA to Discuss CAP-1002 to Treat Duchenne Muscular Dystrophy" . GlobeNewswire News Room (Press release). Retrieved 2021-07-01 .
^
"CARsgen Announces Investigational CAR-T Therapy CT053 Granted RMAT Designation by the U.S. FDA for R/R Multiple Myeloma" . BioSpace . Retrieved 2021-07-01 .
^
"Cartesian Therapeutics Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for Descartes-08 for the Treatment of Myasthenia Gravis" . Cartesian Therapeutics . Retrieved 2024-05-23 .
^
"Cellerant Therapeutics, Inc. Announces FDA Grants Regenerative Medicine Advanced Therapy (RMAT) Designation for romyelocel-L to Prevent Infections During Neutropenia" . Cellerant Therapeutic . 2018-07-02. Archived from
the original on 2021-07-09. Retrieved 2021-07-01 .
^ Coralea.
"Gene-editing therapy CTX001™ is granted RMAT status by FDA for severe β-thalassaemia and SCD" . www.ithanet.eu . Retrieved 2021-07-01 .
^
"Duke researcher's drug RVT-802 receives pioneering FDA regenerative medicine designation – Duke OTC" . Archived from
the original on 2021-07-09. Retrieved 2021-07-01 .
^ ExCellThera (2019-04-23).
"ExCellThera's lead technology, ECT-001, receives FDA Regenerative Medicine Advanced Therapy (RMAT) designation" . GlobeNewswire News Room (Press release). Retrieved 2021-07-01 .
^
"Castle Creek Biosciences: D-Fi Gene Therapy" . Castle Creek Biosciences, Inc . Retrieved 2021-07-01 .
^ Tucker, Nicole (May 8, 2020).
"FDA Grants RMAT Designation to Ilixadencel in Metastatic RCC" . Targeted Oncology . Retrieved 2021-07-01 .
^ Iovance Biotherapeutics Inc. (2018-10-11).
"Iovance Biotherapeutics Reports Results from FDA End of Phase 2 meeting and Provides Updates About the Company's Clinical Program" . GlobeNewswire News Room (Press release). Retrieved 2021-07-01 .
^
"Magenta Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to MGTA-456 for the Treatment of Inherited Metabolic Disorders – Magenta Therapeutics" . investor.magentatx.com . Retrieved 2021-07-01 .
^
"Medeor Therapeutics' Transplant Immune Tolerance Therapy Receives Regenerative Medicine Advanced Therapy Designation from FDA" . www.businesswire.com . 2020-09-22. Retrieved 2021-07-02 .
^
"Mustang Bio Receives Advanced Therapy Medicinal Product Classification from European Medicines Agency for MB-107 Lentiviral Gene Therapy for X-Linked Severe Combined Immunodeficiency" . AP NEWS . 2020-04-20. Retrieved 2021-07-02 .
^
"Rocket Pharmaceuticals Receives FDA Regenerative Medicine Advanced Therapy (RMAT) and Fast Track Designations for RP-L102 Gene Therapy for Fanconi Anemia" . www.businesswire.com . 2018-11-27. Retrieved 2021-07-02 .
^ Voyager Therapeutics Inc. (2018-06-21).
"Voyager Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted for VY-AADC for the Treatment of Parkinson's Disease" . GlobeNewswire News Room (Press release). Retrieved 2021-07-02 .
^
"Rocket Pharmaceuticals Receives FDA Regenerative Medicine Advanced Therapy Designation for RP-L201 Gene Therapy for Leukocyte Adhesion Deficiency-I" . www.businesswire.com . 2021-03-09. Retrieved 2021-07-02 .
^ Orchard Therapeutics (Europe) Limited (2019-07-29).
"Orchard Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted for OTL-103 for the Treatment of Wiskott-Aldrich Syndrome" . GlobeNewswire News Room (Press release). Retrieved 2021-07-02 .
^
"Novartis' Kymriah® Wins Latest FDA RMAT (42 Announced)" . BioInformant . 2020-04-22. Retrieved 2021-06-25 . [
permanent dead link ]
^ Center for Biologics Evaluation and Research (2021-04-05).
"Cumulative CBER Regenerative Medicine Advanced Therapy (RMAT) Designation Requests Received by Fiscal Year" . FDA .