Sarepta Plunged After Adverse Event Forces Trial Halt in the UK
Published: Feb 12, 2018 By Mark Terry
Sarepta Therapeutics stock dropped about 6 percent on Friday after EP Vantage reported the company had halted its Duchenne muscular dystrophy (DMD) clinical trial for golodirsen in the UK after adverse events.
DMD is a muscle-wasting disease that primarily affects boys, and is typically fatal. It is caused by mutations in the dystrophin gene. Sarepta’s Exondys 51 was approved to treat about 13 percent of DMD patients with a specific mutation, even though the approval by the U.S. Food and Drug Administration (FDA) was controversial, due to efficacy concerns.
One patient in the UK trial suffered from rhabdomyolysis, a painful breakdown of muscle tissue. However, rhabdomyolysis is not uncommon in DMD patients, and the patient in question reportedly fell a day or two before the event.
Sarepta indicated that clinical trial rules in the UK required a stoppage, but an independent review board had looked at the safety data and decided the study could continue. The study is continuing outside the UK, but Sarepta is waiting for the UK to give the go-ahead.
Sarepta’s statement said, “Study 4045-301 (ESSENCE) is a global, randomized double-blind, placebo-controlled study evaluating efficacy and safety in patients with Duchenne muscular dystrophy (DMD) amenable to skipping exons 45 or 53. Patients enrolled in the study at UK study sites have temporarily stopped dosing due to UK specific stopping rules, triggered by one serious adverse event (SAE) that could possibly be related to the investigational drug product. The study remains blinded and the adverse event observed is consistent with those seen in patients with DMD. The safety data from all patients in the ESSENCE trial were reviewed by an independent Data Monitoring Committee (DMC). The DMC deemed that dosing could continue for all patients. However, based on the UK specific stopping rules of the study, the Medicine and Healthcare products Regulatory Agency (MHRA) required that dosing stop at all UK sites. Sarepta is currently submitting an amendment to the MHRA. Following approval from the MHRA, dosing can be reinitiated at the UK sites.”
Joseph Schwartz, an analyst with Leerink, wrote in a note to investors, “We believe the observation is a result of UK regulators exercising extreme caution, and it is important to be cognizant of both the severity of the disease as well as the small patient population that DMD affects.”
Both golodirsen and casimersen are being evaluated by Sarepta in DMD. They are projected to be the next-generation versions of Exondys 51.
Brian Abrahams, an analyst with RBC, indicated in a report that these adverse events happened and were reported three months ago. The patient reportedly went back on golodirsen without any more adverse events.
Schwartz wrote, “Thus, we believe an abundance of regulatory caution seems to be the case here rather than an overt class-effect and we maintain our optimism that both golodirsen and casimersen can be effective and attractive drugs just as Exondys 51 has been thus far.”
There are six patients enrolled in the clinical trial at four sites in the UK. At the other 47 sites worldwide, patients stayed on the treatment.