The EMBARK study is a global phase 3 trial investigating the safety and efficacy of delandistrogene moxeparvovec, a gene therapy for Duchenne muscular dystrophy (DMD) in children aged 4 to 7. Explore the study’s key findings with this brief recap.
The EMBARK study represents a significant advancement in the treatment of Duchenne muscular dystrophy (DMD). This global, phase 3, randomized, double-blind, placebo-controlled trial is evaluating the safety and efficacy of delandistrogene moxeparvovec, a novel gene therapy approach aimed at addressing the underlying cause of DMD by delivering a functional copy of the dystrophin gene to muscle cells, in patients between the ages of 4 and 7.
The primary endpoint of the study was the change from baseline in the North Star Ambulatory Assessment (NSAA) total score at Week 52 following treatment. The NSAA is a measure of motor function in DMD patients.
While the primary endpoint did not reach statistical significance, the EMBARK study demonstrated robust, statistically significant results on all key pre-specified secondary endpoints:
- Time to rise (TTR): Participants treated with delandistrogene moxeparvovec showed a statistically significant improvement in TTR compared to placebo, with an overall reduction of 0.64 seconds (p=0.0025). This effect was consistent across both age subgroups (4-5 years: -0.50 seconds, p=0.0177; 6-7 years: -0.78 seconds, p=0.0291).
- 10-meter walk test: delandistrogene moxeparvovec-treated participants showed a statistically significant improvement in the 10-meter walk test compared to placebo, with an overall difference of 0.42 seconds (p=0.0048).
- Other secondary endpoints: delandistrogene moxeparvovec also demonstrated statistically significant improvements in other key functional measures, including stride velocity 95th centile and time to ascend 4 steps.
In terms of safety, no new safety signals were observed in the EMBARK study, and the safety profile of delandistrogene moxeparvovec was consistent with previous studies. The most common treatment-related adverse events were gastrointestinal events, like vomiting, nausea, and decreased appetite, and pyrexia. Seven participants (11.1 percent) experienced a treatment-related serious adverse event, and there were no clinically significant safety concerns.
However, it's important to note that the EMBARK study is still ongoing, and further research is needed to fully understand the long-term effects and durability of the treatment. Though FDA-approved, delandistrogene moxeparvovec was approved through the Accelerated Approval Pathway, under which the FDA may approve drugs for serious or life-threatening diseases where there is an unmet medical need and the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit to patients, such as improving how patients feel or function or whether they survive longer.
Overall, the EMBARK study represents a significant milestone in the quest to develop effective treatments for DMD. By targeting the underlying cause of the disease and potentially restoring dystrophin function, delandistrogene moxeparvovec holds promise for improving the lives of individuals with DMD and their families. But continued research and clinical trials will be crucial in advancing our understanding the role of this and other gene therapies in the treatment of DMD.
References:
FDA approves first gene therapy for treatment of certain patients with Duchenne muscular dystrophy. U.S. Food and Drug Administration. June 22, 2023. Accessed April 11, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-certain-patients-duchenne-muscular-dystrophy.
Muntoni F, Mercuri E, Schara-Schmidt U, et al. EMBARK, a Phase 3 trial evaluating safety and efficacy of delandistrogene moxeparvovec in DMD: Study design and baseline characteristics. Poster 100. Poster presented at: Muscular Dystrophy Association Clinical and Scientific Conference; March 19-22, 2023.
Sarepta Therapeutics announces topline results from embark, a global pivotal study of ELEVIDYS gene therapy for Duchenne Muscular Dystrophy. Sarepta Therapeutics. October 30, 2023. Accessed April 11, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-topline-results-embark-global-0.
Facebook Comments