Golodirsen, Potential Exon 53 Skipping Therapy for Duchenne, Under Priority Review by FDA

Sarepta Therapeutics announced that the U.S Food and Drug Administration (FDA) has accepted its application for a priority review of golodirsen (SRP-4053), a potential treatment for  Duchenne muscular dystrophy (DMD) patients amenable to exon 53 skipping.  A decision is expected on or around Aug. 19.

Golodirsen is being tested in the ongoing ESSENCE Phase 3 trial (NCT02500381) a global, randomized study in about 220 patients assessing the safety and efficacy of golodirsen and casimersen (SRP-4045), the latter Sarepta’s exon 45 skipping therapy for DMD. The study, whose primary completion date is May 2022, is still recruiting patients at sites across Europe, Australia, Canada and Israel. Its U.S. test sites are no longer enrolling.

Priority review is given to therapies with the potential to improve the treatment of serious conditions when compared to the available standard of care.

Duchenne muscular dystrophy, the most common type of muscular dystrophy, is caused by mutations in the DMD gene, which holds the information to produce dystrophin, a protein that supports and protects the muscle fibers. The lack of dystrophin leads to susceptible muscle fibers that damage easily.

Golodirsen is an exon-skipping therapy for patients amenable to skipping of exon 53 in the DMD gene, the largest gene in the human genome. (Exons are sections of a gene that contain the information to produce a part of the protein; the DMD gene has 79 exons.)

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With this approach, golodirsen allows the production of a smaller but functional version of dystrophin, addressing the underlying cause of DMD.

“If approved, golodirsen will serve up to another 8 percent of the Duchenne community, bringing us closer to helping as many Duchenne patients as possible,” Doug Ingram, president and CEO of Sarepta, said in a press release.

“We look forward to working with the FDA toward advancing this important therapy and rapidly bringing it to individuals with Duchenne who are amenable to exon 53 skipping.”

The application is supported by a Phase 1/2 clinical trial (NCT02310906) that evaluated the safety, tolerability, and efficacy of golodirsen in 25 DMD patients. Trial results showed that treated patients had significantly increased levels of functional dystrophin compared to patients who did not have exon 53 mutations.

Exondys 51 (eteplirsen), also by Sarepta, is the first disease-modifying treatment for  Duchenne MD. It was FDA approved in 2016 for patients amendable to exon 51 skipping, which represents about 13 percent of all DMD patients.

Other clinical trials into Duchenne treatments sponsored by Sarepta can be found by visiting this link.