- Sarepta Therapeutics has disclosed positive data from a small trial of a drug meant to be a more potent successor to its marketed Duchenne muscular dystrophy treatment Exondys 51, announcing Monday the experimental drug resulted in stronger production of a key muscle-building protein that Duchenne patients lack.
- Sarepta reported a worrisome side effect alongside treatment, however. Reduced magnesium levels, which can lead to heart damage and seizures, were observed in two of the four patients Sarepta reported data from. Executives said the side effect went away after the patients received oral magnesium, and believe that such supplements can keep the condition from occurring in the future.
- The data may help reassure investors that Sarepta can build a sustainable business treating Duchenne even if its most closely watched project, a gene therapy for the rare disorder, disappoints in clinical trials. That gene therapy, called SRP-9001, failed to significantly improve patient motor function in a clinical trial readout in January, although more results are due this year.
Sarepta has built a portfolio of Duchenne medicines by developing treatments that help patients produce a shortened form of the protein dystrophin. The hope is doing so can help slow the progression of the disease, which often leaves patients wheelchair-bound in their teens.
The actual amount of protein each of Sarepta's approved drugs helps to produce, however, is small and it's unclear whether treatment leads to significant functional benefits for patients. The company is hoping that a newer type of technology can boost those results and require less frequent dosing.
Sarepta has a slate of six drugs in development using the newer technology, and its first attempt is a treatment called SRP-5051. The drug is intended for the same patients as Exondys 51 and is administered less frequently. It also may be more potent than Exondys, which is infused once weekly and helps patients produce less than 1% of normal levels of dystrophin.
The data revealed on Monday are from four patients treated with SRP-5051 who received a once monthly infusion of 30 milligrams per kilogram of body weight. Dystrophin levels were measured after the third dose at 12 weeks.
Sarepta reported that dystrophin levels were an average of 6.6% of normal in the four patients, although that number was inflated by one participant who received five doses before getting a muscle biopsy because of COVID-19 related trial disruptions.
Citing research indicating dystrophin levels can rise over time as patients continue treatment, Sarepta executives said they believe SRP-5051 can help patients get to more than 10% of normal dystrophin, which could dramatically alter their disease course.
Those gains will need to be balanced against the side effects Sarepta reported, which were rated as "Grade 4" adverse events, meaning they were serious and potentially life-threatening. While Sarepta executives weren't certain why SRP-5051 caused the side effect, they said on a conference call Monday that the drug may interfere with proteins that transport magnesium across cell membranes.
The problems were resolved with supplements, however, which gives Sarepta confidence they can be handled in clinical practice. RBC Capital Markets analyst Brian Abrahams wrote that the side effect is "potentially manageable in [the] context of severe disease but may garner increased regulatory scrutiny."
Sarepta executives said they plan to discuss the findings with the Food and Drug Administration and other regulatory agencies to help develop a trial that can be used to support approval.
Asked whether this trial would directly compare SRP-5051 with Exondys 51 to determine if the newer drug has any functional benefit for patients, CEO Doug Ingram said, "We'll have a good robust discussion with [the FDA] about things like protocol — the idea of head-to-head is an interesting one. It's certainly one that teams talked about I don't know if we'll end up landing on that or not."
Ingram added that the early-stage clinical trials for the two drugs measured dystrophin at different time points, making a head-to-head trial trickier to design.
Sarepta shares rose 6% in early trading Monday.