Sarepta Therapeutics has broken free from an FDA hold—put in place this June—on its phase 2 Duchenne muscular dystrophy (DMD) clinical trial.
The FDA originally put part B of Sarepta’s trial—dubbed Momentum—on hold this summer after learning of a serious adverse event in which a participant suffered low magnesium, clinically known as hypomagnesemia. The trial aimed to assess SRP-5051, also known as vesleteplirsen, as a treatment for patients with DMD who are amenable to exon 51 skipping. SRP-5051 can interfere with reabsorption of magnesium, and subjects in the study were taking supplements to counter the risk.
But in a relatively swift turnaround, the company announced Sept. 6, that the hold has been lifted after the FDA took a good look at Sarepta’s risk mitigation and safety monitoring plan for the trial. Sarepta is now adjusting its global trial protocol to include expanded monitoring of urine biomarkers.
“We will implement the changes in the protocol to resume dosing in the U.S. as quickly as possible,” said Louise Rodino-Klapac, Ph.D., Sarepta’s EVP and chief scientific officer. “Our monitoring plan is designed to mitigate the risks of hypomagnesemia. Momentum has continued enrolling participants outside the U.S., and we remain on track to complete enrollment by the end of 2022.”
Around 20% of patients in earlier studies of SRP-5051 experienced grade 3 or 4 hypomagnesemia. Sarepta had previously developed a management plan and observed a decline in grade 2 hypomagnesemia cases during part B of the trial.
The adverse event tied to the FDA hold occurred eight days after a patient in part B was randomized to the high-dose cohort. The patient had grade 3 hypomagnesemia, grade 4 potassium deficiency, muscular cramps and mild to moderate tingling of the extremities.
Without hospitalizing the patient, doctors gave intravenous bolus of magnesium and sent the patient home on increased magnesium and potassium supplementation. Levels of magnesium returned to normal after three days, with no evidence of complications, the company said.
Now, as the multi-arm, ascending dose trial resumes, Sarepta aims to enroll up to 60 participants between ages 7 to 21 across the U.S., Canada and Europe.
Sarepta's shares were down 3% mid-morning Tuesday on the news.