Regenerative Medicine Advanced Therapy (RMAT) is a designation given by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

to drug candidates intended to treat serious or life-threatening conditions under the

21st Century Cures Act The 21st Century Cures Act is a United States law enacted by the 114th United States Congress in December 2016 and then signed into law on December 13, 2016. It authorized $6.3 billion in funding, mostly for the National Institutes of Health. The ...

. A RMAT designation allows for accelerated approval based surrogate or intermediate

endpoint An endpoint, end-point or end point may refer to: * Endpoint (band), a hardcore punk band from Louisville, Kentucky * Endpoint (chemistry), the conclusion of a chemical reaction, particularly for titration * Outcome measure, a measure used as an e ...

s. RMAT goes beyond

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

features by allowing for accelerated approval of drugs based on surrogate endpoints. A surrogate endpoint is a

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...

that substitutes for a direct endpoint, such as clinical benefit.

Legal background

Section 3033 of the

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 The United States Federal Food, Drug, and Cosmetic Act (abbreviated as FFDCA, FDCA, or FD&C) is a set of laws passed by the United States Congress in 1938 giving authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of f ...

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 In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specifi ...

antitumor therapies, may also qualify as regenerative medicine therapies.

Effect

A RMAT designation includes all benefits of the

Fast Track The fast track is an informal English term meaning "the quickest and most direct route to achievement of a goal, as in competing for professional advancement". By definition, it implies that a less direct, slower route also exists. Fast track or F ...

and

designations. In addition, it opens up early interactions between the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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 A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discove ...

, where recruiting a sufficiently large cohort for pre-marketing

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s 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

Statistics

In 2020, the FDA received 34 requests for RMAT status, of which 12 (35.3%) were granted. RMAT designated drugs include the novel

therapy Kymriah and betibeglogene autotemcel for

beta thalassemia Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to cl ...

. 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 Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek). The autologous tissue (also called autogenous, autogenei ...

allogeneic Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, o ...

cell therapy Cell therapy (also called cellular therapy, cell transplantation, or cytotherapy) is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-c ...

products, including

therapies.

References