An investigational gene therapy for Duchenne muscular dystrophy (DMD), called SRP-9001 micro-dystrophin, was given fast track designation by the U.S. Food and Drug Administration (FDA) its developer, Sarepta Therapeutics, announced in a press release.
Fast track status is given to therapies with the potential to treat serious diseases and fill unmet medical needs; it is intended to speed their development and potential review.
SRP-9001 has also been recognized as a rare pediatric disease treatment by the FDA, and given orphan drug status in the United States, the European Union, and Japan. All these recognitions support its development and testing.
DMD is caused by mutations in the gene DMD that encodes for dystrophin, a protein critical for muscles to work as they should. These mutations result in little or no production of a functional dystrophin protein.
A gene therapy for DMD would, ideally, deliver a non-mutated — healthy — version of the DMD gene to the muscle cells, allowing these cells to produce the dystrophin protein. However, the DMD gene is the largest single gene in the human genome, and difficult to deliver to cells.
Researchers at Nationwide Children’s Hospital (who initially developed SRP-9001, and licensed their gene therapy program to Sarepta) designed a smaller version of the gene meant to produce a smaller but working form of dystrophin — a “micro-dystrophin” protein. This gene is delivered to muscle cells using an engineered virus, and genetic modifications were made to ensure appropriate gene expression — essential for protein production — in muscle cells.
Preclinical studies in mouse models of DMD demonstrated that the investigational gene therapy markedly increased dystrophin levels and muscle function.
Recently announced one-year data from an ongoing Phase 1/2 clinical trial, called Study-101 (NCT03375164), testing the safety of a single intravenous infusion of SRP-9001 in four boys with DMD (ages 4 to 7) were promising.
The investigational gene therapy showed a good safety profile, with reported adverse events mild or moderate in intensity. The most common was vomiting after treatment. Levels of gamma-glutamyltransferase — a marker of liver damage — were moderately elevated in three boys, but returned to normal with corticosteroid treatment.
Secondary goals, looking for early signs of efficacy, were also promising. SRP-9001 resulted in widespread expression of micro-dystrophin in muscle tissue, lower levels of creatine kinase (a marker of muscle damage), and improved motor abilities. This study, which opened in January 2018, is due to conclude in April 2021.
A Phase 2 clinical trial, called Study-102 (NCT03769116), is also assessing the gene therapy’s safety and efficacy. Study-102 has enrolled 41 boys with DMD (ages 4 to 7), who are being given a single SRP-9001 infusion or that of a placebo. After 48 weeks of evaluation, participants will be eligible for a 96-week extension study. Results from Study-102 are expected in early 2021.
Both trials are sponsored by Sarepta.
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