Delandistrogene moxeparvovec (Elevidys), a gene therapy for Duchenne muscular dystrophy (DMD), recently received FDA approval, but a new research review published in Neurology examines clinical trials with mixed results and lingering safety concerns.
The first-in-class gene therapy aims to slow the disease’s progression by delivering a shortened version of the dystrophin gene — the protein missing in DMD patients — using a modified virus. It was first granted accelerated approval in 2023 for ambulatory boys aged 4 to 5 and received full FDA approval for boys aged 4 and up a year later, including those who are no longer walking.
But while the science is promising, recent studies reviewed by the American Academy of Neurology (AAN) suggest that the benefits of the therapy may be limited and also raise concerns about potential risks.
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Researchers analyzed four trials with data on 134 boys aged 4 to 8, the majority of whom were able to walk. They noted the results showed mixed evidence with many limitations. In one trial of four boys, for example, motor function improved with treatment, but the sample size was small and lacked a placebo group. A subsequent phase 2 trial involving 41 boys failed to show statistically significant improvement across the whole group, but boys aged 4 to 5 demonstrated modest improvements in motor skills.
The EMBARK Phase 3 placebo-controlled study, the largest trial to date with 126 participants, failed to meet its primary goal of a meaningful motor function improvement after one year. Some secondary measures, like the time it took boys to stand up or walk 10 meters, showed slight improvements, but were not statistically significant.
Although the treatment is generally well tolerated, it may involve some risks. Vomiting was the most commonly reported side effect, and cases of myocarditis (inflammation of the heart muscle), acute liver injury and immune-mediated myositis also occurred. To try to prevent or manage these side effects, corticosteroids can be used starting the day before treatment and continuing for at least two months.
As delandistrogene moxeparvovec may now be actively prescribed in the United States and other countries after FDA approval, the researchers say providers should be aware of its potential risks and the need to monitor for immune-related side effects.
“Additional clinical trials and careful collection of real-world evidence from treated patients will be essential to establish short-term and long-term effectiveness and inform understanding of benefits and risks of delandistrogene moxeparvovec across the lifespan,” the researchers concluded.
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