Sarepta’s Duchenne muscular dystrophy (DMD) drug candidate SRP-5051 (vesleteplirsen) was placed on clinical hold by the US Food and Drug Administration (FDA) due to a serious adverse event of hypomagnesemia that developed during the MOMENTUM clinical trial. The FDA is now requesting information from the company about all cases of hypomagnesemia.
“Patient safety is always our top priority,” said Louise Rodino-Klapac, PhD, executive vice president and chief scientific officer of Sarepta Therapeutics, in a press release.
“The hypomagnesemia was identified through lab tests conducted as part of the monitoring outlined in the protocol of the MOMENTUM study and is similar to previously observed cases of hypomagnesemia in clinical trials of SRP-5051. The hypomagnesemia was transient and patients’ magnesium levels returned to normal following additional supplementation.”
SRP-5051 is a next-generation peptide-conjugated phosphorodiamidate morpholino oligomer being developed for the treatment of patients with DMD amenable to exon 51 skipping.
Read more about exon skipping for DMD
MOMENTUM is a phase 2, multiarm, ascending dose clinical trial evaluating the safety, tolerability, and efficacy of SRP-5051 in 60 patients with DMD, aged 7 to 21 years in the US, Canada, and Europe.
In 2021, Sarepta reported results from the trial showing that after 12 weeks of treatment with SRP-5051 at a dose of 30 mg/kg every month, let to 18 times the exon skipping and 8 times the dystrophin production as weekly eteplirsen (Exondys 51) for 24 weeks. Hypomagnesemia was also identified but this was reversible.
According to the company, MOMENTUM remains on track to complete enrollment by the end of the year. “We will work to share information with FDA with the goal of resuming screening and dosing in the U.S. as quickly as possible,” Dr. Rodino-Klapac said.
DMD is caused by a mutation in the DMD gene, which disrupts the reading frame of the gene or introduces a premature stop codon. The result is no production of functional dystrophin protein, which is essential for muscle health. Around 13% of patients with DMD have a mutation that makes them amenable to skipping exon 51, thereby restoring the gene’s reading frame.
Sarepta Therapeutics provides update on SRP-5051 for the treatment of Duchenne muscular dystrophy. News release. Sarepta Therapeutics; June 23, 2022.
Two-part study for dose determination of SRP-5051 (vesleteplirsen) (Part A), then dose expansion (Part B) in participants with Duchenne muscular dystrophy amenable to exon 51-skipping treatment (MOMENTUM). US National Library of Medicine. Updated June 7, 2022. Accessed June 27, 2022.