Roche will begin a new international Phase 3 trial for its controversial Duchenne muscular dystrophy gene therapy drug Erebidis in a new push for approval in Europe. Rather than relying on patient groups to make a passionate case, the company aims to dispel doubts through the rigor of its clinical studies.
The Swiss drugmaker will begin a new phase 3 trial after the European Medicines Agency’s medicines examiner last year did not support approval of Erevidis for ambulatory Duchenne patients.
Following feedback from the EMA and the Duchenne community, Roche plans to generate additional placebo-controlled data necessary for resubmission to the EMA, again targeting outpatients, the company announced Thursday.
“The launch of this new study reflects Roche’s commitment to the Duchenne community and our determination to make this disease-modifying therapy available to ambulatory boys in Europe and around the world,” Levi Garraway, MD, Roche’s chief medical officer and head of global product development, said in an April 16 statement. “Our confidence is rooted in robust long-term data demonstrating the durable efficacy and safety of Erebidis, and our experience treating more than 1,000 ambulatory boys around the world.”
Elevidys is currently approved for outpatient DMD patients in the United States and is marketed by its original developer, Sarepta Therapeutics. FDA approval was based on the Phase 3 Embark study, which failed to meet its primary endpoint and showed no statistically significant improvement in motor function with Erebidis compared to placebo for one year.
In its previous negative opinion on Erevidis, the EMA noted that the 0.65 point difference between gene therapy and placebo on the Northstar Outpatient Assessment score of 34 was not statistically significant.
Sarepta has used long-term data to argue for the value of Erebidis. These include three-year results published in January showing a 4.39 point improvement compared to a propensity-weighted untreated external control group.
The new Phase 3 study will once again compare Erebidis to a placebo, but this time over a 72-week period in about 100 outpatient boys. The primary endpoint was change in rise time from the bed, which is an important prognostic factor for future disease progression. In the previous Embark trial, researchers initially recorded an improvement of 0.64 seconds during the randomization phase. When compared to Sarepta’s 3-year external control, the effect was 6.05 seconds.
“Erevidis is approved in only nine countries and remains a significant unmet need for outpatient DMD patients around the world,” a Roche spokesperson said in a statement to Fierce Pharma. “This study is designed to ensure that all participants have a pathway to treatment, which we believe will positively contribute to recruitment.”
Initially, participants in the placebo group will be eligible to receive Erevidis after an initial 72-week period, the spokesperson said.
In the United States, Erebidis previously boasted a broad label that covered both outpatient and ambulatory patients, even though the majority of its evidence was from outpatients. But last year, reports of the deaths of two non-ambulatory patients with severe liver damage raised major safety concerns. Roche first stopped distributing Erevidy for outpatient use in former U.S. territories and then stopped shipments to some countries altogether.
Last year, Sarepta was in a tug-of-war with the FDA. After intense political and patient advocacy opposition to a total ban, authorities ultimately allowed Erebidis to remain on the market, but only for outpatient treatment.
Meanwhile, Sarepta is testing enhanced immunosuppressive therapy to manage hepatotoxicity of Erebidis in outpatients, but the potential regulatory pathways there remain unclear.
As for Roche, the Swiss drugmaker is currently focused on outpatient patients, where “the benefit-risk ratio is positive and data shows durable treatment effects,” a company spokesperson said. Although current data do not support a favorable profile in the non-ambulatory group, the results of Sarepta’s new Cohort 8 of the Endeavor trial will inform future planning, the spokesperson said.
