Sarepta Therapeutics’ Duchenne muscular dystrophy (DMD) gene therapy, Elevidys, failed on the primary endpoint in a pivotal Phase III study, the company announced yesterday. The endpoint is a measure of motor function, called the North Star Ambulatory Assessment.
Despite this setback, the company said the results of the trial were positive and, on a conference call, chief scientific officer Louise Rodino-Klapac, PhD, said they plan to file for a label expansion to treat “all DMD patients” and to convert the drug’s accelerated approval into a standard approval.
The drug received accelerated approval in late June of this year, when it became the first and only gene therapy available for DMD. But that approval was only in pediatric patients four through five years of age. The EMBARK study of Elevidys (delandistrogene moxeparvovec-rokl) included patients with Duchenne muscular dystrophy between the ages of four through seven years.
“The results of EMBARK, our double-blind, placebo-controlled trial, support the conclusion that Elevidys modifies the trajectory of Duchenne and benefits patients across age groups living with this ferociously degenerative disease,” Doug Ingram, Sarepta’s president and chief executive officer, said in a press release. “The results favored Elevidys across all endpoints in the study, including achieving statistical significance on all pre-specified key secondary endpoints and in each age subgroup of the key secondary endpoints. Indeed, passing five seconds on time to rise is the strongest predictor of early loss of ambulation and in EMBARK, Elevidys reduced those odds over 52 weeks by greater than 90 percent.”
He added that, “Based on the EMBARK results, we intend to move swiftly to request an update to expand the labeled indication to treat all patients. Importantly, we have shared the EMBARK topline results with FDA leadership and they have confirmed that, based on the totality of the evidence, they are open to such label expansion if supported by review of the data, and that they intend to proceed rapidly with consideration of the submission.”
In the study, Elevidys-treated patients improved 2.6 points on their North Star Ambulatory Assessment total score 52 weeks after treatment compared to 1.9 points in placebo-treated patients. The difference of 0.65-points between treated and placebo groups did not reach statistical significance (n=125; p=0.24).
The company says all key pre-specified functional secondary endpoints demonstrated “robust evidence for a clinically meaningful treatment benefit that was consistent across age groups in Elevidys-treated patients compared to placebo at 52 weeks.
These include: All other timed functional endpoints—including stride velocity 95th centile and time to ascend four steps—demonstrated consistent treatment benefit in favor of Elevidys. Full results from EMBARK will be shared at future medical meetings and publication will be pursued in a medical journal.
“The strong prognostic power of time to rise, and the particular importance of the five second milestone in predicting functional decline and future loss of ambulation, is clearly demonstrated in natural history. In EMBARK, the reduction in patients progressing past this milestone when treated with Elevidys is highly clinically relevant,” said Craig McDonald, MD, professor and chair of the UC Davis Health Department of Physical Medicine and Rehabilitation, and an investigator in the EMBARK study.
Sarepta is responsible for regulatory approval and commercialization of Elevidys in the U.S., as well as manufacturing. Roche is responsible for regulatory approvals across the rest of the world. Together, the companies are implementing a joint clinical development plan.
