Regenerative medicine advanced therapy

Last updated

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]

Contents

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]

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

  1. meet the definition of a regenerative medicine therapy,
  2. intend to treat, modify, reverse or cure a serious condition, and
  3. 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

  1. previously agreed-upon surrogate or intermediate endpoints, or
  2. 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to comply with the requirements for accelerated approval, the RMAT designation and the benefits conferred by it can be withdrawn ( 21 CFR 601.43 ).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
NameDesigneeTypeBiological targetTherapeutic 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

Related Research Articles

<span class="mw-page-title-main">Biogen</span> Pharmaceutical company

Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, United States specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide. Biogen operates in Argentina, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Mexico, Netherlands, Poland, Sweden, and Switzerland.

Sarepta Therapeutics, Inc. is a medical research and drug development company with corporate offices and research facilities in Cambridge, Massachusetts, United States. Incorporated in 1980 as AntiVirals, shortly before going public the company changed its name from AntiVirals to AVI BioPharma soon with stock symbol AVII and in July 2012 changed name from AVI BioPharma to Sarepta Therapeutics and SRPT respectively. As of 2023, the company has four approved drugs.

<span class="mw-page-title-main">Fast track (FDA)</span> US FDA designation for investigational drugs

Fast track is a designation by the United States Food and Drug Administration (FDA) of an investigational drug for expedited review to facilitate development of drugs that treat a serious or life-threatening condition and fill an unmet medical need. Fast track designation must be requested by the drug company. The request can be initiated at any time during the drug development process. FDA will review the request and attempt to make a decision within sixty days.

Astellas Institute for Regenerative Medicine is a subsidiary of Astellas Pharma located in Marlborough, Massachusetts, US, developing stem cell therapies with a focus on diseases that cause blindness. It was formed in 1994 as a company named Advanced Cell Technology, Incorporated (ACT), which was renamed to Ocata Therapeutics in November 2014. In February 2016 Ocata was acquired by Astellas for $379 million USD.

Teprotumumab, sold under the brand name Tepezza, is a medication used to treat adults with thyroid eye disease, a rare condition where the muscles and fatty tissues behind the eye become inflamed, causing the eyes to bulge outwards.

Flexion Therapeutics, Inc. is an American biopharmaceutical company based in Burlington, Massachusetts that is focused on the discovery, development and commercialization of novel, local therapies for the treatment of patients with musculoskeletal conditions, beginning with osteoarthritis (OA), the most common form of arthritis.

Arcturus Therapeutics Holdings Inc. is an American RNA medicines biotechnology company focused on the discovery, development and commercialization of therapeutics for rare diseases and infectious diseases. Arcturus has developed proprietary lipid nanoparticle RNA therapeutics for nucleic acid medicines including small interfering RNA (siRNA), messenger RNA (mRNA), gene editing RNA, DNA, antisense oligonucleotides, and microRNA.

Adverum Biotechnologies, Inc., formerly known as Avalanche Biotechnologies, is a publicly traded clinical stage gene therapy company located in Redwood City, California. The company is targeting unmet medical needs for serious ocular and rare diseases, including wet age-related macular degeneration.

<span class="mw-page-title-main">Trilaciclib</span> Chemical compound

Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.

<span class="mw-page-title-main">Umbralisib</span> Chemical compound

Umbralisib, sold under the brand name Ukoniq, is an anti-cancer medication for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL). It is taken by mouth.

Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat B-cell lymphoma and follicular lymphoma.

bluebird bio, Inc., based in Somerville, Massachusetts, is a biotechnology company that develops gene therapies for severe genetic disorders.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

<span class="mw-page-title-main">Ultragenyx</span> American biopharmaceutical company

Ultragenyx is an American biopharmaceutical company involved in the research and development of novel products for treatment of rare and ultra-rare genetic diseases for which there are typically no approved treatments and high unmet medical need. The company works with multiple drug modalities including biologics, small molecule, gene therapies, and ASO and mRNAs in the disease categories of bone, endocrine, metabolic, muscle and CNS diseases.

<span class="mw-page-title-main">CRISPR Therapeutics</span> Swiss-American biotechnology company

CRISPR Therapeutics AG is a Swiss–American biotechnology company headquartered in Zug, Switzerland. It was one of the first companies formed to utilize the CRISPR gene editing platform to develop medicines for the treatment of various rare and common diseases. The company has approximately 500 employees and has offices in Zug, Switzerland, Boston, Massachusetts, San Francisco, California and London, United Kingdom. Its manufacturing facility in Framingham, Massachusetts won the Facilities of the Year Award (FOYA) award in 2022. The company’s lead program, exagamglogene autotemcel, or exa-cel, was granted regulatory approval by the US Food and Drug Administration (FDA) in December 2023.

Infigratinib, sold under the brand name Truseltiq, is an anti-cancer medication used to treat cholangiocarcinoma.

OTL-103 (GSK-2696275) is a gene therapy for Wiskott–Aldrich syndrome, a rare primary immunodeficiency caused by mutations in the gene that codes for Wiskott–Aldrich syndrome protein (WASp). It was developed by Orchard Therapeutics in conjunction with GlaxoSmithKline. It is currently undergoing Phase I/II of clinical trials that are expected to conclude in October 2025.

RVT-802 is a medication being developed by Enzyvant Therapeutics Ireland Limited for the treatment of congenital athymia, especially in the context of DiGeorge syndrome.

Valoctocogene roxaparvovec, sold under the brand name Roctavian, is a gene therapy used for the treatment of hemophilia A. It was developed by BioMarin Pharmaceutical. Valoctocogene roxaparvovec is made of a virus (AAV5) that has been modified to contain the gene for factor VIII, which is lacking in people with hemophilia A. It is an adeno-associated virus vector-based gene therapy. It is given by intravenous infusion.

Atidarsagene autotemcel, sold under the brand name Libmeldy among others, is a gene therapy treatment for metachromatic leukodystrophy developed by Orchard Therapeutics. It contains an autologous CD34⁺ cell enriched population that contains haematopoietic stem and progenitor cells transduced using a lentiviral vector encoding the human arylsulfatase A (ARSA) gene.

References

  1. ↑ "Regenerative Medicine Advanced Therapy Designation". Food and Drug Administration. Retrieved 25 June 2021.
  2. ↑ 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.
  3. ↑ 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.
  4. 1 2 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.
  5. ↑ 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.
  6. 1 2 "Regulatory intelligence: Update on regenerative medicine advanced therapies designations". Endpoints News. Retrieved 2021-06-25.
  7. ↑ 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.
  8. ↑ "Abeona Announces FDA Grants RMAT Designation to ABO-102 Gene Therapy in MPS IIIA". Abeona Therapeutics Inc. Retrieved 2021-07-01.
  9. ↑ "Regenerative Medicine Advanced Therapy Designation Granted to ADP-A2M4 for Synovial Sarcoma". Journal of Oncology Navigation & Survivorship. 2019-12-11.
  10. ↑ "FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma". OncLive. Retrieved 2021-07-01.
  11. ↑ "AlloVir Secures Latest RMAT Designation for Viralym-M". BioInformant. 2019-06-12. Retrieved 2021-07-01.{{cite web}}: Check |url= value (help)[ permanent dead link ]
  12. ↑ "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.
  13. ↑ Asterias Biotherapeutics (2017-10-02). "Asterias Announces Two Significant Developments for Spinal Cord Injury Program". GlobeNewswire News Room (Press release). Retrieved 2021-07-01.
  14. ↑ 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.
  15. ↑ "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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ "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.
  19. ↑ "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.
  20. ↑ "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.
  21. ↑ Coralea. "Gene-editing therapy CTX001™ is granted RMAT status by FDA for severe β-thalassaemia and SCD". www.ithanet.eu. Retrieved 2021-07-01.
  22. ↑ "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.
  23. ↑ 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.
  24. ↑ "Castle Creek Biosciences: D-Fi Gene Therapy". Castle Creek Biosciences, Inc. Retrieved 2021-07-01.
  25. ↑ Tucker, Nicole (May 8, 2020). "FDA Grants RMAT Designation to Ilixadencel in Metastatic RCC". Targeted Oncology. Retrieved 2021-07-01.
  26. ↑ 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.
  27. ↑ "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.
  28. ↑ "Medeor Therapeutics' Transplant Immune Tolerance Therapy Receives Regenerative Medicine Advanced Therapy Designation from FDA". www.businesswire.com. 2020-09-22. Retrieved 2021-07-02.
  29. ↑ "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.
  30. ↑ "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.
  31. ↑ 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.
  32. ↑ "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.
  33. ↑ 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.
  34. ↑ "Novartis' Kymriah® Wins Latest FDA RMAT (42 Announced)". BioInformant. 2020-04-22. Retrieved 2021-06-25.{{cite web}}: Check |url= value (help)[ permanent dead link ]
  35. ↑ Center for Biologics Evaluation and Research (2021-04-05). "Cumulative CBER Regenerative Medicine Advanced Therapy (RMAT) Designation Requests Received by Fiscal Year". FDA.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.