FDA Lifts Hold on Sarepta's DMD Trial Following Protocol Adjustments
Courtesy of Sarepta Therapeutics
The FDA removed the clinical hold on Sarepta Therapeutics' investigational Duchenne muscular dystrophy (DMD) therapy Tuesday after the company agreed to adjust its clinical trial protocols to include expanded monitoring of urine biomarkers.
The FDA ordered a halt in June to the United States arm of the Phase II trial assessing the safety and efficacy of SRP-5051 (vesleteplirsen) after a serious safety signal was detected. A trial participant developed a dangerously low level of serum magnesium, a condition known as hypomagnesemia.
The FDA lifted the hold after Cambridge, Mass.-based Sarepta agreed to adjust the trial's protocols to expand the 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, the company's executive vice president and chief scientific officer, in a press release. “Our monitoring plan is designed to mitigate the risks of hypomagnesemia."
Sarepta spokesperson Tracy Sorrentino told BioSpace the trial’s adjusted protocols will also require spot urine assessments of patients prior to visits. Sorrentino said the new requirement should “help minimize intra-patient variability of the urine biomarkers.”
The trial, dubbed MOMENTUM, continued to enroll patients in Canada and the European Union not covered by the FDA's hold. Sarepta said it expects to complete enrollment in part B of the 60-patient study by the end of the year.
Part A of the trial, completed last year, showed that 12 weeks of monthly SRP-5051 infusions led to an eight-fold increase in dystrophin in the skeletal muscle compared to eteplirsen. Cases of reversible hypomagnesemia were also detected in part A.
Part B's protocols include the lab tests that detected the serious hypomagnesia case. The patient also reported mild-to-moderate tingling of the extremities and muscle cramps and was found to have low serum potassium levels. Protocol-prescribed supplementation resolved the patient's symptoms within three days, including the return to normal magnesium levels.
In the U.S., DMD patients have very limited treatment options.
SRP-5051 is a next-generation peptide-conjugated phosphorodiamidate morpholino oligomer. The treatment is being developed for patients with DMD who are amenable to exon 51 skipping.