Eteplirsen

Sarepta Therapeutics is stopping development of vesleteplirsen, an experimental exon 51-skipping therapy for Duchenne muscular dystrophy patients with certain mutations. It’s also halting work on all programs that use the same peptide, R&D head Louise Rodino-Klapac said in an analyst call Wednesday. That includes approaches for exons 45 and 53, a spokesperson told Endpoints News in an email. The decision to stop developing vesleteplirsen was due to “information available to date, including the risk-benefit of the program, feedback from the FDA, and the evolving therapeutic landscape for Duchenne,” Sarepta said in its third-quarter earnings report. There are cases of persistent hypomagnesemia — or abnormally low magnesium — even after discontinuing treatment, Rodino-Klapac added. The FDA had informed the biotech that the accelerated approval pathway “was not open” with the current information on the drug, she said. Vesleteplirsen, also known as SRP-5051, was a next-generation version of Exondys 51, Sarepta’s first exon-skipping drug that received accelerated approval in 2016. In Phase 2 study results shared in January, Sarepta reported a mean 5.17% dystrophin expression in 20 patients who received a high dose of the therapy and a 2.81% dystrophin expression in 20 patients who received a low dose of the therapy. On Wednesday, Sarepta also reported $181 million in revenue from its Duchenne gene therapy Elevidys, which beat Wall Street’s expectations. There’s also $9.5 million in royalties from Roche, which is commercializing Elevidys outside the US. The FDA in June granted Elevidys a controversial expanded label , making a majority of people with Duchenne muscular dystrophy ages 4 and older eligible for the drug.

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. '