Sarepta Halts SRP-5051 Program for Duchenne Over Benefit-Risk Concerns

Sarepta Therapeutics has announced its decision to stop the development of its investigational treatment for Duchenne muscular dystrophy (DMD), SRP-5051 (vesleteplirsen), due to ongoing safety concerns and changes in the treatment landscape, including the approval of its DMD gene therapy Elevidys (delandistrogene moxeparvovec). This decision coincides with the company reporting robust third-quarter sales for Elevidys.

CEO Douglas Ingram explained that the decision was made after careful consideration, ensuring it was the best choice for the patient community and stakeholders. The primary reason for discontinuing SRP-5051 was the persistent issue of low magnesium levels in some patients during clinical trials. Although these events were "medically manageable," the risk-benefit analysis led the company to halt dosing in the Phase II MOMENTUM study.

Louise Rodino-Klapac, Sarepta's chief scientific officer, emphasized that patient safety is the company's top priority. She noted that despite treatment discontinuation, persistent hypomagnesemia was observed in a small number of patients, which influenced the decision to end the studies. The FDA had previously placed a clinical hold on the SRP-5051 study in 2022 due to a serious adverse event of hypomagnesemia in one patient. This hold was lifted after Sarepta agreed to expand its monitoring of urine biomarkers.

Earlier this year, Sarepta reported promising data from the MOMENTUM study, indicating that SRP-5051, when dosed every four weeks, significantly increased dystrophin expression and exon skipping compared to the company's approved antisense oligonucleotide Exondys 51 (eteplirsen), which requires weekly dosing. However, Rodino-Klapac mentioned that the FDA was not willing to allow an accelerated approval pathway for SRP-5051 based on its current profile.

In addition to discontinuing SRP-5051, Sarepta has decided to scrap its broader peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) projects, as these therapies utilize the same cell-penetrating peptide.

Despite these setbacks, Sarepta recorded $181 million in Elevidys revenues in the third quarter, surpassing consensus estimates by approximately $16 million, as noted by BMO Capital Markets. Analysts highlighted that Sarepta's established success in the DMD field continues to drive significant growth for Elevidys, with potential for uptake across all DMD patients, regardless of age or ambulatory status.

This development emphasizes Sarepta's commitment to prioritizing patient safety while navigating the evolving treatment landscape for DMD. The company's strategic decisions reflect a focus on delivering effective therapies while managing risks associated with new treatments.