Sarepta Therapeutics Announces Positive Data from Phase 2 Study in Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 51

CAMBRIDGE, Mass. — Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced positive data from Part B of the MOMENTUM study (Study SRP-5051-201), a global, Phase 2, multi-ascending dose clinical trial of SRP-5051 (vesleteplirsen) that enrolled patients aged 8 to 21 years. SRP-5051 is a next-generation peptide phosphorodiamidate morpholino oligomer (PPMO) treatment for patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping.

Data from Part B of MOMENTUM 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%, and mean exon skipping of 11.11% at 28 weeks (n=20). Consistent dystrophin expression was seen in ambulatory (4.76%, n=11) and non-ambulatory (5.67%, n=9) 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, Ph.D., 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. As the leader in Duchenne, Sarepta is committed to advancing meaningful treatments for those with Duchenne and other rare diseases where there is unmet need.”

High dose results at 28 weeks (~30 mg/kg, dosed every four weeks, n=20):

• 5.17% mean dystrophin expression as measured by western blot
• 4.53% mean change from baseline, P < 0.0001
• Mean exon skipping of 11.11%, as measured by digital drop polymerase chain reaction (ddPCR), and a mean change from baseline in exon skipping of 10.07%
• The changes from baseline 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 eteplirsen at 24 weeks (mean dystrophin expression of 0.82%, mean exon skipping of 0.59%, n=16).

Low dose results at 28 weeks (~20 mg/kg, dosed every four weeks, n=20):

• 2.81% mean dystrophin expression as measured by western blot
• 1.60% mean change from baseline, P= 0.0012
• Mean exon skipping of 2.47%, as measured by ddPCR, and a mean change from baseline in exon skipping of 2.00%
• The changes from baseline 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 dystrophin production delivered by SRP-5051 in the MOMENTUM study is very encouraging. Importantly, with effective supplementation and monitoring, we have not seen additional complications from the hypomagnesemia,” said Eugenio Mercuri, M.D., Ph.D., head of the Neuromuscular Unit, Catholic University, Rome, Italy, and an investigator in the study. “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.”

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.

 

About SRP-5051 (vesleteplirsen)

SRP-5051 is an investigational agent using Sarepta’s PPMO chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. SRP-5051 is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally shortened dystrophin protein. PPMO is Sarepta’s next-generation chemistry platform designed around a proprietary cell-penetrating peptide conjugated to the PMO backbone, with the goal of increasing tissue penetration, increasing exon skipping, and significantly increasing dystrophin production. Around 13% of Duchenne patients have mutations that make them amenable to skipping exon 51. If successful, the PPMO offers the potential for improved efficacy and less frequent dosing for patients.

 

About MOMENTUM (Study SRP-5051-201)

MOMENTUM is a global, Phase 2, multi-arm, ascending dose study of SRP-5051, infused every four weeks, and will assess dystrophin protein levels in skeletal muscle tissue following SRP-5051 treatment. The study will also assess safety and tolerability. Part B enrolled 40 participants, both ambulant and non-ambulant, between the ages of 8 to 21 at sites in the U.S., Canada, and Europe.

 

About EXONDYS 51

EXONDYS 51 (eteplirsen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion, or “skipping”, of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

EXONDYS 51 is indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 51 skipping.

This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in some patients treated with EXONDYS 51. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

EXONDYS 51 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.

 

About Sarepta Therapeutics

Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing.