Sarepta's Second Muscular Dystrophy Drug Shows Greater Promise in Phase II

Sarepta_Courtesy of Sarepta

Photo courtesy of Sarepta.

Sarepta Therapeutics announced Monday that its next-generation peptide phosphorodiamidate morpholino oligomer (PPMO) candidate, SRP-5051, showed promise in a Phase II trial when used as a treatment for Duchenne muscular dystrophy in patients amenable to exon 51 skipping. The announcement of the findings made the company’s stock shoot up 9% to $77.

Sarepta is investigating SRP-5051 as a follow-up to its other Duchenne muscular dystrophy drug, Exondys 51 (eteplirsen). The company’s currently marketed eteplirsen for the muscle-wasting disorder isn’t exactly a robust competitor – the drug only produces modest dystrophin amounts and received controversial approval in 2016 after leaders with the U.S. Food and Drug Administration (FDA) overruled its scientists. 

The company’s PPMO chemistry and exon-skipping technology developed SRP-5051 to skip exon 51 found in the dystrophin gene. According to the company, the candidate binds to exon 51 in dystrophin pre-mRNA, subsequently leading to exclusion of the exon during the processing of mRNA. Likewise, skipping up the exon facilitates the production of a truncated dystrophin protein. Approximately 13% of patients with Duchenne muscular dystrophy present with genetic mutations, making them susceptible to exon 51 skipping. 

In Part A of Sarepta’s recent global, multi-ascending dose MOMENTUM trial (Study 5051-201), investigators discovered that after only three monthly doses of SRP-5051 30 mg/kg, biopsies examined at a median 12-week follow-up showed 18 times the exon skipping as well as eight times the dystrophin production as eteplirsen dosed weekly for 24 weeks. 

Additionally, the researchers found consistently higher exon skipping and dystrophin production with SRP-5051 30 mg/kg compared with 20 mg/kg. Patients who took SRP-5051 experienced hypomagnesemia, but supplemental magnesium was able to resolve these cases. 

“Even at an early timepoint of 12 weeks and after as few as only three doses, these data confirm the potential of Sarepta’s next-generation PPMO platform to be a step order improvement over our current PMO platform, and to profoundly impact the course of Duchenne,” said Sarepta’s President and Chief Executive Officer, Doug Ingram, in a statement. “While we saw exceptional expression after only a few initial doses, our models predict that we will exceed dystrophin expression levels of 10% of normal or greater over time with SRP-5051.” 

Ingram noted that Part A of the company’s MOMENTUM trial has now been completed, and Sarepta is working on plans to discuss the findings with regulatory agencies to gain insights on how to support accelerated approval of the therapy.

Back in late February, the FDA approved Sarepta’s Duchenne muscular dystrophy injection therapy, Amondys 45 (casimersen), for use in patients with a confirmed mutation of the gene amenable to exon 45 skipping. Approval was made based on data from a placebo-controlled trial that show the therapy increased dystrophin production in skeletal muscle. A statement made by the agency noted that casimersen represents the first agency-approved targeted therapy for patients with this mutation type. 

"Developing drugs designed for patients with specific mutations is a critical part of personalized medicine," said Eric Bastings, M.D., Deputy Director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, in a statement. "Today's approval of Amondys 45 provides a targeted treatment option for Duchenne muscular dystrophy patients with this confirmed mutation."

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