Positive Results from Phase 2 SRP-5051 Trial for Duchenne MD Patients

Sarepta Therapeutics, a frontrunner in precision genetic medicine for rare diseases, has unveiled promising results from the MOMENTUM study, which focused on SRP-5051 (vesleteplirsen), a novel PPMO treatment for Duchenne muscular dystrophy (DMD) patients suitable for exon 51 skipping. The Phase 2 clinical trial involved subjects aged 8 to 21 years and demonstrated that SRP-5051, when administered at a target dose of approximately 30 mg/kg monthly, led to a mean dystrophin expression of 5.17% and a mean exon skipping of 11.11% after 28 weeks.

The findings from Part B of the MOMENTUM study indicate that SRP-5051, dosed monthly, significantly outperforms eteplirsen, which is dosed weekly, in terms of increasing dystrophin and exon skipping levels. Louise Rodino-Klapac, Ph.D., Sarepta's executive vice president and head of research and development, highlighted the positive benefit-risk profile of SRP-5051 and the company's eagerness to engage with the FDA to discuss the outcomes and future plans. Sarepta's commitment to advancing effective treatments for DMD and other rare diseases with unmet needs is reaffirmed.

In the high-dose group at 28 weeks, SRP-5051 showed 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 after 24 weeks. The low-dose group also displayed a 4.3-fold increase in dystrophin expression and a 4.9-fold increase in exon skipping compared to the same weekly dose of eteplirsen.

Eugenio Mercuri, M.D., Ph.D., principal investigator of the study and head of the Neuromuscular Unit at Catholic University in Rome, emphasized the encouraging results of SRP-5051 in inducing dystrophin production. He also noted that hypomagnesemia, a condition previously identified in patients treated with SRP-5051, was effectively managed through prophylactic magnesium supplementation as part of the study protocol.

The study also reported seven serious treatment-emergent adverse events, including hypomagnesemia and hypokalemia, all of which were addressed with appropriate measures, and no treatment-related discontinuations were reported.

SRP-5051 is an investigational agent leveraging Sarepta's PPMO chemistry and exon-skipping technology, designed to bind to exon 51 of the dystrophin pre-mRNA and induce the exclusion of this exon during mRNA processing. The PPMO platform is intended to enhance tissue penetration and exon skipping, thereby increasing dystrophin production. Approximately 13% of DMD patients have mutations that are amenable to exon 51 skipping, presenting a significant potential patient population for SRP-5051.

The MOMENTUM study is a global Phase 2 trial that assesses dystrophin protein levels in skeletal muscle tissue following SRP-5051 treatment, along with safety and tolerability. It has enrolled 40 participants, both ambulant and non-ambulant, between the ages of 8 to 21, across the U.S., Canada, and Europe.

Sarepta Therapeutics is dedicated to developing precision genetic medicine for rare diseases, with a robust pipeline driven by gene therapy, RNA, and gene editing platforms. The company holds leadership positions in DMD and limb-girdle muscular dystrophies and is actively progressing over 40 programs in various stages of development.