EMA Initiates Review of Roche's Elevidys for Duchenne Muscular Dystrophy
Key Insights
The EMA has begun reviewing Roche's Elevidys, a gene therapy for Duchenne muscular dystrophy (search) (DMD), potentially the first DMD gene therapy in Europe.
The application is based on Phase 3 EMBARK trial data, which showed clinically meaningful benefits in key secondary functional endpoints.
Elevidys is already approved in the US and several other countries for ambulatory patients with DMD, targeting the underlying genetic cause.
The European Medicines Agency (EMA) has validated and initiated review of the marketing authorisation application (MAA) for Elevidys™ (delandistrogene moxeparvovec), a gene therapy developed by Roche for treating ambulatory patients aged 3-7 years with Duchenne muscular dystrophy (search) (DMD). This announcement, made on June 24, 2024, signals a potential breakthrough in the treatment landscape for this devastating genetic disorder.
Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, emphasized the urgent need for treatments that can modify the disease course and preserve muscle function. “Duchenne is a devastating muscle-wasting disease with no cure. Treatments that can change the disease course and preserve muscle function are urgently needed,” said Garraway. “Roche is committed to bringing Elevidys to the children who need it and we welcome the EMA’s review of the filing submission.”
Clinical Data Supporting the Application
The Elevidys MAA is primarily based on data from the pivotal Phase 3 EMBARK study, a global, randomised, double-blind, placebo-controlled trial involving patients with Duchenne aged 4 through 7 years. While the EMBARK study did not meet its primary endpoint, comprehensive analysis of the data revealed clinically meaningful benefits in key secondary functional endpoints. Specifically, Elevidys-treated patients demonstrated statistically significant improvements in time to rise from floor (p<0.05) and the 10-minute walk/run test (p<0.05). Furthermore, a clinically meaningful and statistically significant improvement was observed in stride velocity, measured using a wearable device (Syde®), a novel digital endpoint qualified by the EMA.
Additional supportive data comes from the ENDEAVOR open-label study, which includes both ambulatory and non-ambulatory patients across various age groups, and a Phase I/II study providing long-term efficacy, durability, safety, and biological data.
Expanding the Scope of Treatment
Roche is also conducting two additional studies, ENVOL (Phase 2, boys under 4) and ENVISION (Phase 3, older ambulatory and non-ambulatory patients), to potentially expand the label for Elevidys to include a broader range of DMD patients.
Current Approval Status and Collaboration
Elevidys has already received approval in the United States, Qatar, Kuwait, UAE, Oman, and Bahrain. Roche is responsible for commercializing Elevidys outside the US as part of a 2019 collaboration agreement with Sarepta Therapeutics. The FDA recently converted the accelerated approval to a traditional approval and expanded the label to include ambulatory individuals aged four and older with a confirmed mutation in the DMD gene, and also granted accelerated approval for non-ambulatory Duchenne patients.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (search) is a rare, genetic, muscle-wasting disease affecting approximately 1 in 5,000 boys worldwide. It is caused by mutations in the DMD gene, leading to a deficiency in the dystrophin (search) protein, which is crucial for muscle fiber strength and protection. The progressive muscle damage leads to loss of ambulation, respiratory and cardiac dysfunction, and a reduced life expectancy, averaging around 28 years.
Elevidys (delandistrogene moxeparvovec) is designed to address the underlying cause of Duchenne by delivering a shortened, functional version of the dystrophin (search) gene to skeletal, respiratory, and cardiac muscles via a one-time intravenous infusion. It is contraindicated in patients with deletions in exons 8 and/or 9 of the DMD gene.