New analysis tracks Elevidys outcomes 3 years after treatment
EMBARK follow-up compares gene therapy patients with natural history data
Three years after receiving the gene therapy Elevidys (delandistrogene moxeparvovec-rokl) in a clinical trial, boys with Duchenne muscular dystrophy (DMD) are showing sustained improvements in physical function compared with what would be expected without treatment, according to new data announced by Sarepta Therapeutics, Elevidys’ developer.
“ELEVIDYS is the first gene therapy for Duchenne to show a dramatic shift in disease trajectory out to three years consistent with earlier long-term data extending up to five years. This is long-term data in a robust, controlled clinical dataset that demonstrates the power of a disease-modifying therapy targeting the underlying cause of Duchenne,” Louise Rodino-Klapac, PhD, president of research and development and technical operations at Sarepta, said in a company press release.
Elevidys is currently approved in the U.S. to treat DMD patients ages 4 and older who are able to walk. That approval was based largely on data from the Phase 3 EMBARK clinical trial (NCT05096221), which tested the gene therapy against a placebo in more than 120 ambulatory boys with DMD and showed the treatment led to improvements in some measures of physical function.
Earlier EMBARK data showed lasting motor gains
Sarepta previously announced two-year data showing patients given Elevidys in EMBARK had better long-term motor outcomes than untreated DMD patients. Now, the company has announced an analysis comparing three-year follow-up data from 52 Elevidys-treated patients with outcomes from 73 untreated boys with DMD drawn from natural history studies or a prior trial. The two groups were matched based on factors such as age and motor function scores at the time of treatment.
Results of the new analysis showed that scores on a motor function measure called the North Star Ambulatory Assessment were significantly better in Elevidys-treated patients, by 4.39 points on average compared with the external control group. The time to rise from a lying position and the time to walk or run 10 meters (about 33 feet) were also significantly faster, by 6.05 seconds and 2.7 seconds, respectively.
My patients know, based on the dialogue that I have with them routinely, that my primary objective for them is to pursue dystrophin-restoring therapy as the foundation for their treatments.
Sarepta highlighted that, at three years post-Elevidys, these patients are on average about 9 years old — a time when people with DMD typically begin to experience more rapid loss of motor function. According to the company, the difference between patients given Elevidys and natural history controls has been growing over time, which suggests the gene therapy may help slow disease progression.
“As a pediatric neurologist, I spend time with families who are doing everything they can to help their children stay strong in the face of Duchenne,” said Crystal Proud, MD, an investigator in the EMBARK study at Children’s Hospital of The King’s Daughters. “The EMBARK results give us a clearer picture of how treatment with ELEVIDYS can make a meaningful difference over time, and they reflect what I see in clinical practice – helping boys perform everyday movements, such as standing, walking and running with greater strength and speed than what we expect as Duchenne progresses without a disease-modifying treatment.”
What causes Duchenne muscular dystrophy
DMD is caused by mutations in the gene that encodes dystrophin, a protein essential for keeping muscle cells intact. Elevidys is designed to deliver a gene that produces a shortened but functional form of dystrophin in muscle cells.
When the U.S. Food and Drug Administration (FDA) fully approved Elevidys for ambulatory DMD patients ages 4 and older in 2024, it also granted conditional authorization for patients 4 and older who could not walk. However, after two nonambulatory patients died from liver-related side effects following treatment, the FDA withdrew that conditional authorization.
Liver injury associated with Elevidys is thought to result from immune reactions to the viral vector used to deliver the gene therapy. Although the vector is engineered not to cause infection, it can still trigger inflammation in the liver. Sarepta is now testing whether adding an immune-suppressing drug called sirolimus may help reduce this risk.
“We have a lot to learn about the potential benefit of adding sirolimus to our treatment paradigm, and of course, we’d like to try to mitigate risk as best we can,” Proud said in a Sarepta webinar, noting that data from these ongoing clinical tests will help to guide best practices for Elevidys administration going forward.
Proud also said that she hasn’t seen any notable declines in patients’ interest in Elevidys due to the reported safety issues and changes to the therapy’s prescribing label. “My patients know, based on the dialogue that I have with them routinely, that my primary objective for them is to pursue dystrophin-restoring therapy as the foundation for their treatments.”
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