Sarepta Reports Positive Data from a Phase 2 Study of Investigational PPMO Treatment for DMD Amenable to Skipping Exon 51

Rare Daily Staff

Sarepta Therapeutics reported data from a phase 2 trial that supports a positive benefit-risk profile for SFP-5051, or vesleteplirsen, a next generation treatment for patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping.

Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, is a rare and life-threatening neuromuscular disorder characterized by progressive muscle dysfunction, ultimately leading to loss of ambulation, respiratory failure, and fatality. SRP-5051, a next-generation version of Sarepta’s Exondys 51, is a peptide phosphorodiamidate morpholino oligomer (PPMO) treatment for patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping.

Data from Part B of the MOMENTUM study, a global, phase 2, multi-ascending dose clinical trial of SRP-5051 that enrolled patients aged 8 to 21 years, found that at the higher, target dose, approximately 30 mg/kg dosed every four weeks, SRP-5051 resulted in mean dystrophin expression of 5.17 percent, and mean exon skipping of 11.11 percent at 28 weeks. Consistent dystrophin expression was seen in ambulatory (4.76 percent) and non-ambulatory (5.67 percent) participants at 28 weeks. Hypomagnesemia has previously been identified in patients taking SRP-5051 and was managed and monitored through prophylactic magnesium supplementation as part of the study protocol.

“SRP-5051 dosed every four weeks is showing substantially higher increases in dystrophin and exon skipping compared to eteplirsen dosed weekly,” said Louise Rodino-Klapac, executive vice president, chief scientific officer, and head of research and development, Sarepta Therapeutics. “The data suggest a favorable benefit-risk profile for SRP-5051 and we look forward to discussing the results and next steps with FDA.”

The changes from baseline for the high dose participants represent a 12.2-fold increase in dystrophin expression and a 24.6-fold increase in exon skipping compared to a weekly 30 mg/kg dose of Exondys 51 at 24 weeks.

The changes from baseline at 28 weeks for patients who received a low dose (~20 mg/kg, dosed every four weeks) represent a 4.3-fold increase in dystrophin expression and a 4.9-fold increase in exon skipping compared to a weekly 30 mg/kg dose of eteplirsen at 24 weeks.

“The results with SRP-5051 to date suggest it could play an important role in the treatment of Duchenne patients with a confirmed exon 51-amenable mutation,” said Eugenio Mercuri, head of the Neuromuscular Unit, Catholic University, Rome, Italy, and an investigator in the study.

There were seven serious, treatment-emergent adverse events in MOMENTUM Part B, four serious events of hypomagnesemia and three serious cases of hypokalemia. Hypomagnesemia has been seen in earlier clinical studies of SRP-5051 and, throughout MOMENTUM Part B, supplemental magnesium was administered prophylactically. No treatment-related discontinuations occurred in the study.

Photo: Louise Rodino-Klapac, executive vice president, chief scientific officer, and head of research and development, Sarepta Therapeutics