Roche is launching a new global phase 3 trial for the controversial Duchenne muscular dystrophy gene therapy Elevidys in another push for European approval. Rather than relying on patient groups to make an impassioned plea, the company aims to put doubts to rest with the rigor of a clinical study.
The Swiss pharma is launching a new phase 3 after drug reviewers at the European Medicines Agency last year refused to support approval of Elevidys for Duchenne patients who are able to walk.
Following feedback from the EMA and the Duchenne community, Roche plans to generate additional placebo-controlled data required for a resubmission with the agency again in the ambulatory population, the company said Thursday.
“The initiation of this new study reflects Roche’s commitment to the Duchenne community and our resolve to make this disease-modifying therapy available to ambulatory boys in Europe and around the world,” Levi Garraway, M.D., Ph.D., 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 showing the durable efficacy and safety of Elevidys, alongside the experience of treating more than a thousand ambulatory boys worldwide.”
Elevidys is currently approved for ambulatory DMD patients in the U.S., where it’s sold by its original developer, Sarepta Therapeutics. The FDA approval was based on the phase 3 Embark trial, which missed its primary endpoint, failing to show a statistically significant improvement in motor function with Elevidys versus placebo at one year.
In its previous negative opinion on Elevidys, the EMA noted that the gene therapy’s 0.65-point difference with placebo in the 34-point North Star Ambulatory Assessment scores was not statistically significant.
Sarepta has argued for Elevidys’ value using long-term data. These include three-year results unveiled in January showing a 4.39-point improvement when compared with a propensity-weighted untreated external control group.
The new phase 3 will again compare Elevidys to placebo, but this time over 72 weeks in about 100 ambulatory boys. The primary endpoint is the change in Time to Rise from the floor, which is an important prognostic factor of future disease progression. Previously, in the Embark trial, investigators initially recorded an improvement of 0.64 seconds in the randomized phase. The effect was 6.05 seconds in Sarepta’s three-year comparison against external control.
“With Elevidys approved in only nine countries, significant unmet need remains for ambulatory DMD patients globally,” a Roche spokesperson said in a statement to Fierce Pharma. “The study will be designed to ensure that all participants have a path to treatment, which we consider will positively contribute to recruitment.”
Participants initially in the placebo group will be eligible to receive Elevidys after the primary 72-week period, the spokesperson noted.
In the U.S., Elevidys had previously boasted a broad label covering both ambulatory and non-ambulatory patients, despite the bulk of its evidence coming from the ambulatory population. But major safety concerns emerged last year with the reports of two deaths of non-ambulatory patients involving severe liver injury. Roche first stopped distribution of Elevidys for non-ambulatory patients in its ex-U.S. territories, then paused shipments completely in some countries.
Last year, Sarepta got into a tug-of-war with the FDA. Following intense political and patient advocacy pushback against a full-on ban, the agency eventually allowed Elevidys to remain on the market, but only to treat ambulatory patients.
Meanwhile, Sarepta is testing an enhanced immunosuppression regimen to manage Elevidys’ liver toxicity in non-ambulatory patients, although its potential regulatory path there remains unclear.
As for Roche, its spokesperson said the Swiss drugmaker is currently focused on the ambulatory population, “where the benefit-risk is positive and data have shown a durable treatment effect.” While current data do not support a favorable profile in the non-ambulatory group, results from Sarepta’s new cohort 8 of the Endeavor trial will inform any future plans, the spokesperson said.