Encouraging Phase II Outcomes for Advanced DMD Therapy

Sarepta Therapeutics has recently announced encouraging outcomes from a Phase II clinical trial of SRP-5051 (vesleteplirsen), a novel drug designed to address Duchenne muscular dystrophy (DMD) in patients who are candidates for exon 51 skipping. The Massachusetts-based company has unveiled further insights from the Momentum study's part B, which examined the efficacy of SRP-5051, a PPMO treatment, in individuals aged eight to 21.

The study revealed that administering a 30 mg/kg dose of SRP-5051 at four-week intervals led to a mean dystrophin expression of 5.17% and a mean exon skipping of 11.11% after 28 weeks. Sarepta highlighted that the findings demonstrated a consistent level of dystrophin expression across both ambulatory and non-ambulatory patients. The high-dose variant of the drug exhibited a 4.53% mean change from baseline at the 28-week mark, with a p-value significantly less than 0.0001. In contrast, a lower dosage of 20 mg/kg resulted in a 2.81% mean dystrophin expression and a 1.60% mean change, yielding a p-value of 0.0012.

Louise Rodino-Klapac, Sarepta's Chief Scientific Officer, stated that SRP-5051, when dosed every four weeks, showed a substantially higher increase in dystrophin and exon skipping compared to weekly dosing of eteplirsen. She also noted the data pointed to a favorable benefit-risk profile for SRP-5051 and expressed eagerness to discuss the results and subsequent steps with the FDA.

Despite the positive results, the trial did report seven serious treatment-emergent adverse events, including four instances of severe hypomagnesemia and three cases of hypokalemia. However, Sarepta has indicated that hypomagnesemia was present throughout the trial, and no treatment-related discontinuations were recorded. Eugenio Mercuri, the study's lead investigator and head of the neuromuscular unit at Catholic University in Rome, Italy, commented that with proper supplementation and monitoring, no additional complications from hypomagnesemia were observed. He also suggested that SRP-5051 could play a significant role in treating patients with DMD who have a confirmed exon 51-amenable mutation.

In June 2023, Sarepta's gene therapy, Elevidys (delandistrogene moxeparvovec-rokl), received FDA approval as the first-ever treatment for DMD. The therapy, previously known as SRP-9001, was granted accelerated approval for ambulatory patients aged four to five with a confirmed mutation in the DMD gene.