Boys with DMD given Elevidys 2 years ago still showing motor gains
Trial data point to positive changes in Duchenne's trajectory with gene therapy
Two years after receiving the gene therapy Elevidys (delandistrogene moxeparvovec-rokl), motor function continues to improve in boys with Duchenne muscular dystrophy (DMD) who entered a global clinical trial able to walk.
That’s according to top-line findings from part two of the Phase 3 EMBARK trial (NCT05096221), which evaluated Sarepta Therapeutics‘ approved gene therapy in more than 120 boys with DMD ages 4 to 7.
Significant motor function gains also were seen one year after treatment among children who began with a placebo in part one of EMBARK and a year later were treated with Elevidys, compared with an external and untreated DMD control group.
“As a neuromuscular medicine specialist who has seen patients with Duchenne muscular dystrophy for over three decades, I’ve witnessed firsthand the positive impact of gene therapy on the trajectory of Duchenne,” Craig McDonald, MD, an EMBARK study investigator and professor and chair of the University of California at Davis’ department of physical medicine and rehabilitation, said in a company press release.
Duchenne gene therapy working to produce microdystrophin in muscle cells
“These longer-term results are even more striking when compared to external control given the progressive nature of the disease,” McDonald said. “The efficacy of Elevidys gives me great hope as we continue to follow these patients and see others treated in the clinical setting.”
DMD is caused by mutations that disrupt the production of dystrophin, a protein that normally cushions muscle fibers against damage. Without functional dystrophin, muscle cells accumulate excess damage over time, ultimately driving disease symptoms of muscle weakness and wasting.
Elevidys (previously called SRP-9001), administered via an infusion into the bloodstream, is designed to deliver to muscle cells a gene for a shortened but functional version of dystrophin called microdystrophin. Sarepta developed the therapy and markets it in the U.S., while Roche markets it outside the U.S.
The one-time therapy is fully approved for DMD patients in the U.S., ages 4 and older, who can walk (ambulatory). It’s also available under accelerated approval in the U.S. for those who cannot walk, with full approval depending on additional data to confirm its benefit in this population.
Findings in the crossover EMBARK study largely supported Elevidys’s approvals. In the first part, participants were randomly assigned to the gene therapy or a placebo and followed for one year. Those given the placebo switched to Elevidys and vice versa in its second part, with all followed for another year.
The study’s main goal was to evaluate how gene therapy affected scores on the North Star Ambulatory Assessment (NSAA), a standardized motor function measure in children with DMD who can walk. Although top-line data showed it failed to meet this primary goal, Elevidys significantly outperformed the placebo in several key secondary measures of motor function.
Boys given single infusion showed gains in motor tests for second year
Top-line findings now cover two-year results of the trial’s first part and the one-year findings from its second part. To assess efficacy, outcome data were compared to a matched and untreated external control group of patients, who participated in five separate DMD studies.
Two years after Elevidys treatment, statistically significant and clinically meaningful improvements were seen across three motor function measures: NSAA, the time to rise (TTR), and the 10-meter walk/run (10MWR) tests, compared with the external group. Notably, these differences increased from year one to year two across all three functional measures.
Biopsies taken 64 weeks after dosing (about 15 months) also showed consistent and sustained production of microdystrophin compared with week 12 biopsies. MRIs of skeletal muscle, or those attached to bones, found minimal progression in underlying muscle damage.
“After two years of treatment with Elevidys, we are seeing multiple sustained benefits in the day-to-day lives of these young boys,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a separate press release. “These results, which include improvements in standing, walking and running, represent meaningful progress.”
DMD patients who received the placebo in the first part and subsequently were treated with Elevidys also showed significant functional gains after one year. Despite being one year older than the trial’s initial treatment group (average age of 7.18 vs. 5.98 years), these patients showed clinically meaningful and statistically significant functional benefits for the NSAA, TTR, and 10MWR tests compared with the external controls, Sarepta reported.
Phase 3 trial of Elevidys enrolling patients able or unable to walk
“We’re very encouraged to see the results from Part 2 of EMBARK as they further elucidate the impact Elevidys has on disease progression,” said Louise Rodino-Klapac, PhD, executive vice president, head of R&D, and chief scientific officer at Sarepta. “The consistency and totality of evidence supporting a long-term and clinically meaningful treatment benefit with Elevidys continues to grow.”
No new safety signals have been reported so far. According to the companies, detailed results from the second part of the EMBARK study will be shared at future medical meetings and discussed with health authorities.
The global Phase 3Â ENVISION trial (NCT05881408) is assessing Elevidys in a wide range of DMD patients who can and cannot walk at study entry. Recruitment is ongoing at sites across Europe and in Australia, Israel, Hong Kong, Japan, and Taiwan; its U.S. sites are enrolled.
Elevidys also is approved, with certain restrictions, for Duchenne patients in Brazil, Israel, the United Arab Emirates, Qatar, Kuwait, Bahrain, and Oman. Requests for approval have been submitted to regulatory authorities in the European Union, Japan, and several other countries, Roche reported.
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