Roche initiates new phase 3 trial to secure European approval for Elevidys

UK—Roche is making another push for European approval of Elevidys, its gene therapy for Duchenne muscular dystrophy, by launching a new phase 3 clinical trial.

The Swiss pharmaceutical company aims to address concerns raised by European regulators through additional rigorous clinical data rather than relying solely on advocacy from patient groups.

The European Medicines Agency rejected Elevidys for ambulatory patients last year, citing insufficient evidence of effectiveness.

In response, Roche has designed this new trial to generate the placebo-controlled data that EMA reviewers requested.

The company plans to resubmit its application based on these fresh findings.

“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,” said Levi Garraway, Roche’s chief medical officer and head of global product development, in a statement.

The Challenge of Modest Results

Elevidys currently holds approval in the United States, where original developer Sarepta Therapeutics markets it.

However, the FDA granted approval despite the drug’s phase 3 Embark trial missing its primary target—it failed to demonstrate statistically significant improvement in motor function compared to placebo at one year.

The EMA previously highlighted this shortfall, noting that Elevidys showed only a 0.65-point difference on the 34-point North Star Ambulatory Assessment scale, a difference that lacked statistical significance.

Sarepta countered this criticism by presenting three-year follow-up data from January, which showed a 4.39-point improvement when measured against an external control group of untreated patients.

A different endpoint, new hope

Roche’s upcoming trial will compare Elevidys against placebo over 72 weeks in approximately 100 ambulatory boys.

Notably, the study uses a different primary endpoint: the Time to Rise from the floor, considered a key indicator of future disease progression.

In the original Embark trial, patients receiving Elevidys showed a 0.64-second improvement in this measure, while Sarepta’s external comparison revealed a 6.05-second improvement.

This shift in focus reflects an attempt to demonstrate the therapy’s clinical relevance through a more meaningful measure of daily function.

To ensure successful enrollment, Roche plans to allow participants initially assigned to placebo to receive Elevidys after the 72-week evaluation period.

A company spokesperson confirmed that “the study will be designed to ensure that all participants have a path to treatment.”

Safety concerns reshape the landscape

Safety issues have significantly shaped Elevidys’ recent history.

Last year, reports emerged of two deaths involving non-ambulatory patients who experienced severe liver injury.

These incidents prompted Roche to suspend distribution for non-ambulatory patients, and the FDA subsequently narrowed the drug’s approved use to ambulatory patients only.

Currently, Elevidys has received approval in only nine countries globally, leaving substantial unmet need in the broader Duchenne patient population.

Sarepta is separately developing enhanced immunosuppression strategies to manage liver toxicity, though its regulatory pathway for non-ambulatory patients remains uncertain.