Sarepta Submits BLA for First-Ever Duchenne Muscular Dystrophy Gene Therapy

After running its Duchenne Muscular Dystrophy (DMD) gene therapy, SRP-9001, through the clinical trial gauntlet, Sarepta Therapeutics submitted a Biologics License Application (BLA) to the FDA in hopes of gaining accelerated approval. With optimistic-looking data from its first set of clinical trials, Sarepta already enrolled participants in a confirmatory trial for the drug, which the FDA would require if it approves the drug on the accelerated approval pathway. 

SRP-9001’s Development So Far

Sarepta designed SRP-9001 in partnership with Roche to treat ambulant patients (those who can walk independently) with DMD. The disease is a severe muscle-wasting disease caused by mutations that prevent dystrophin production in muscle tissue, which is vital to muscle production and movement. Patients typically present symptoms around two to three years old, and most patients become wheelchair-bound by ten to twelve. As DMD progresses, patients often require assisted ventilation, and even with optimal care, patients seldom live past 40 years old due to cardiac and respiratory complications. 

SRP-9001 is an investigational gene transfer therapy designed to deliver the drug to muscle tissue, which could promote the production of certain components of dystrophin. Sarepta embarked on three studies called the ENDEAVOR studies to evaluate SRP-9001’s safety and efficacy based on a surrogate endpoint consisting of an increased expression of SRP-9001 dystrophin protein. 

If SRP-9001 receives accelerated approval, it will mark Sarepta’s fourth DMD therapy with the status and the first gene therapy for DMD patients. Sarepta’s other products approved through the accelerated pathway include Exondys 51, Vyondys 53, and Amondys 45. 

President and CEO at Sarepta, Doug Ingram, said, “Sarepta’s BLA submission for an accelerated approval of SRP-9001 is a significant milestone in our quest to intervene with urgency on behalf of the children we serve. If approved, SRP-9001 will be the first gene therapy available for Duchenne patients.”

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Planning for Postmarket Requirements and Commitments

As part of the accelerated approval pathway, the FDA requires companies to perform confirmatory trials, proving a drug’s safety and efficacy with primary endpoints instead of surrogate endpoints. Sarepta appears ready for the challenge because it has offered up its already-enrolled EMBARK study to serve as the confirmatory trial if SRP-9001 gains accelerated approval. 

The EMBARK trial is a global, randomized, double-blind, placebo-controlled study. Instead of the surrogate endpoint of SRP-9001 dystrophin expression, the trial will monitor the change in North Star Ambulatory Assessment (NSAA). The NSAA is a rating scale that measures motor abilities in ambulant children with DMD. 

Sarepta’s previously approved drugs all received accelerated approval and are undergoing confirmatory trials to meet the FDA’s postmarket requirements and commitments. So far, none of the three have fulfilled all criteria needed to qualify for regular approval. Two drugs have at least one requirement or commitment listed as submitted or fulfilled, while Exondys 51’s requirements are delayed even though Sarepta projected the projects would be finished by 2018 and 2021. 

SRP-9001 is a gene therapy candidate designed to treat ambulant children with DMD. If the FDA grants the drug accelerated approval, it will mark the first gene therapy available for DMD patients and Sarepta’s fourth DMD-targeting therapy, bolstering their position as leading experts in treating the disease. 

Author

Reed Slater