After serious side effect, Sarepta and FDA realign on next-gen Duchenne drug with trial hold lifted

FDA’s monthslong trial hold on Sarepta Therapeutics’ next-gen Duchenne muscular dystrophy drug is out the door after the biotech and regulator hashed out a new global trial protocol to expand monitoring of urine biomarkers.

The US agency took notice in June after a serious adverse event of low magnesium levels in one patient’s blood — a condition known as hypomagnesemia — was observed in part B of the MOMENTUM trial. The Phase II study is slated to test vesleteplirsen, formerly SRP-5051, in about 60 patients between ages 7 and 21 in the US, Canada and EU.

Patients with mutations amenable to skipping exon 51 account for about 13% of people with DMD, Sarepta said. The company already markets an antisense oligonucleotide for mutations amenable to exon 51 — Exondys 51. Sarepta also markets meds for 53 and 45, known as Vyondys 53 and Amondys 45, respectively.

At the time, and again Tuesday, Sarepta said the global study would still wrap up enrollment by year’s end. The Massachusetts biotech has been enrolling in study sites outside the US during the trial hold, Sarepta said.

Louise Rodino-Klapac

The hold had come as a surprise, SVB Securities analysts wrote back in June, because the biotech had “worked closely with the FDA” on the study’s risk mitigation measures. In a new note Tuesday, SVB analysts said lifting the hold was “another incremental positive for SRPT,” but questions remain about what the expanded monitoring could mean beyond a trial: “it remains to be seen how monitoring may impact use in the real-world; however, we look forward to additional details on the protocol changes.”

“We will implement the changes in the protocol to resume dosing in the U.S. as quickly as possible,” Sarepta CSO Louise Rodino-Klapac said in a statement.

Vesleteplirsen works similarly to Exondys 51 but with a different chemical underpinning. Both drugs target RNA, unlike Sarepta’s gene therapies, which go after DNA. The company has a slate of discovery- and preclinical-stage assets targeting DMD and various exons.

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