Vesleteplirsen

Sarepta Therapeutics has decided to discontinue development of its investigational Duchenne muscular dystrophy (DMD) treatment SRP-5051 (vesleteplirsen), citing persistent safety concerns and an "evolving" treatment landscape, including the approval of its approved DMD gene therapy Elevidys (delandistrogene moxeparvovec). The move comes as the company reported strong third-quarter sales for Elevidys."One never takes lightly the decision to discontinue a programme, but we are confident that our decision is the right one for the patient community and for our stakeholders," stated CEO Douglas Ingram during the company's third-quarter earnings call.Persistently low magnesium levels The main driver behind the SRP-5051 pull-out was the occurrence of persistently low magnesium levels in some patients during clinical testing. Though the events were "medically manageable," the company's risk-benefit analysis ultimately led it to halt dosing in the Phase II MOMENTUM study."The safety and study participants is our highest priority," said Louise Rodino-Klapac, Sarepta's chief scientific officer. "Although events thus far, remained medically manageable in a small number of patients, we saw persistent hypomagnesemia, despite treatment discontinuation and our risk-benefit analysis led us to end the studies."The FDA had previously placed a clinical hold on the SRP-5051 study in 2022 following a serious adverse event of hypomagnesemia in one patient. The hold was lifted roughly two months later when Sarepta agreed to expand its monitoring of urine biomarkers.The programme's prospects appeared to be on the right track. Earlier this year, Sarepta reported promising data from the MOMENTUM study, showing that SRP-5051 dosed every four weeks substantially increased dystrophin expression and exon skipping compared to the company's approved antisense oligonucleotide Exondys 51 (eteplirsen), which is dosed weekly. However, Rodino-Klapac said the FDA "was not open" to allowing an accelerated approval pathway for SRP-5051 "based on the current profile to date."Broader PPMO pipeline scrappedSarepta's decision to discontinue SRP-5051 also extends to the company's broader peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) projects, as the therapies all use the same cell-penetrating peptide.Meanwhile, the company recorded $181 million in Elevidys revenues in the third quarter, beating consensus estimates by about $16 million, according to BMO Capital Markets. "Sarepta's established and successful record in DMD continues to drive significant Elevidys growth, with the potential for uptake across all DMD patients regardless of age or ambulatory status," the analysts wrote. For more, see – Spotlight On: Sarepta reiterates $2 billion forecast for DMD gene therapy in 2025 on back of 'unprecedented progress'.

Dive Brief:Sarepta Therapeutics is giving up on an experimental drug for Duchenne muscular dystrophy as sales rocket for its approved gene therapy for the disease.The decision to discontinue SRP-5051 was based on several factors, company executives told analysts on a conference call Wednesday. Safety concerns, feedback from the Food and Drug Administration and the evolving landscape of Duchenne with the approval of Sareptas gene therapy Elevidys all played a role, Chief Scientific Officer Louise Rodino-Klapac told analysts and investors.Elevidys revenue climbed to $181 million in the third quarter from $122 million in the second quarter, beating analyst estimates of about $160 million. Sarepta also pulled in $9.5 million in royalties from Roche, which sells the gene therapy outside the U.S.Dive Insight:The end of SRP-5051 is disappointing, according to analysts, but Elevidys' trajectory should more than make up for it. Sales of the gene therapy may top $2 billion next year, Leerink Partners analyst Joseph Schwartz wrote in a note to investors.The third-quarter revenue jump for Elevidys came after the FDA expanded the therapys label in late June to make it available to the vast majority of people with Duchenne, a genetic disorder that usually affects boys and steadily causes their muscles to degenerate. Second-quarter sales for the product had fallen below analyst expectations, but executives expressed confidence that growing demand would lead to an uptick in revenue.SRP-5051 is tailored to Duchenne patients who have mutations in exon 51 of the dystrophin gene, and the company saw it as a new-generation treatment to build on its approved therapy, Exondys 51. The drug was designed with an improved form of the exon skipping technology that underlies its predecessor. But testing showed that while SRP-5051 may be more effective than Exondys 51, it also led some patients to suffer from prolonged low levels of magnesium.Originally, company officials thought the condition, known as hypomagnesia, could be managed and monitored, but it persisted in some patients even after they stopped treatment with the drug, Rodino-Klapac said. Now, the company has decided to stop development of SRP-5051 and so-called PPMO drugs like it.Sales of Sareptas three marketed exon-skipping drugs, which include Exondys 51, are likely to continue to grow and wont be affected much by competition from Elevidys until after next year, analysts said. Those medicines generated combined revenue of about $249 million in the third quarter.We support the companys decision to discontinue the development of its PPMO franchise, given its first gene therapy appears to be a commercial success and is well on its way to being a blockbuster product, William Blair analyst Sami Corwin wrote in a note to clients. '