Two Years In, Elevidys Shows Functional Benefit in Older Boys With Duchenne
On September 30, 2026, Sarepta Therapeutics presented new data for Elevidys (delandistrogene moxeparvovec), its gene therapy for Duchenne muscular dystrophy (DMD), at the World Muscle Society Congress. Boys who received the therapy between ages 8 and 12 kept more of their motor function over two years than closely matched boys who were never treated.
The update comes a little over a year after Elevidys faced its most serious crisis. Deaths from acute liver failure in 2025 led to a boxed warning and a narrower label. These new results speak to a different question: does the therapy still help boys who are treated later, when the disease usually starts to speed up?
What Duchenne does to muscle
Duchenne is caused by mutations in the DMD gene on the X chromosome, so it mostly affects boys. The gene makes dystrophin, a large protein that links the internal scaffold of a muscle fiber to the membrane around it and to the tissue outside the cell. Dystrophin keeps the membrane stable while the fiber contracts.
Without dystrophin, muscle membranes are damaged during normal use. Fibers break down faster than they can be repaired, and over time muscle is replaced by scar tissue and fat. Most boys show weakness by age 3 to 5. Many lose the ability to walk in their early teens, and later the disease affects breathing and the heart.
The years from about 7 to 12 are a turning point. Many boys move from a relatively stable phase into steady decline, which makes this a hard window in which to show that a treatment works.
How Elevidys works
The DMD gene is one of the largest in the human genome, far too big to fit inside an adeno-associated virus (AAV) vector. Elevidys delivers a shortened gene instead, which codes for micro-dystrophin. This version keeps the protein's key working regions while dropping much of its repetitive middle section.
The gene travels inside an AAVrh74 vector, given as a single intravenous infusion.
A muscle-specific promoter switches the gene on mainly in skeletal and heart muscle.
Treated fibers make micro-dystrophin, which sits at the membrane and partly takes over dystrophin's stabilizing role.
Because micro-dystrophin is not the full protein, Elevidys is not expected to fully restore muscle. The goal is to slow the loss of function.
What the new data showed
The main analysis pooled 25 boys from the EMBARK and ENDEAVOR studies who were dosed between ages 8 and 12. Researchers compared them with 99 untreated boys from natural history datasets. The groups were matched on the studies' eligibility rules and balanced for factors known to affect how fast Duchenne progresses.
After two years, the treated boys did better on three standard motor tests:
North Star Ambulatory Assessment (NSAA): a 3.32-point advantage on this 34-point scale of everyday motor tasks (p=0.0022).
Time to rise from the floor: a faster rising velocity, with a difference of 0.041 rises per second (p=0.0019).
10-meter walk/run: a speed difference of 0.195 meters per second (p=0.0114).
Sarepta said the differences were also present at one year. "We are seeing functional benefit that's statistically significant at a stage when decline often becomes more pronounced," said Dr. Craig McDonald of UC Davis Health, who presented the analysis.
A second, much smaller analysis looked at nine children treated between ages 2 and 3. At 12 weeks, muscle biopsies showed micro-dystrophin levels averaging 94% of a reference control in one cohort of six children and 73% in a second cohort of three. Sarepta noted these levels were higher on average than in older patients. Treatment of children under 4 remains investigational.
Why the comparison group matters
These results are encouraging, but they come with an important caveat. The treated boys were compared with an external control group, not with boys randomly assigned to placebo in the same trial.
External controls can be carefully matched and still differ in ways that are hard to measure, such as access to physical therapy, steroid dosing, or effort on test day. For that reason, comparisons like this are weaker evidence than a randomized trial.
This matters for Elevidys in particular. Its Phase 3 EMBARK trial in boys aged 4 to 7 did not meet its primary endpoint, the change in NSAA score at 52 weeks, although several secondary measures favored treatment. Much of the case for the therapy has rested on secondary and longer-term results like these.
Safety in context
Sarepta described safety in the new analysis as manageable and consistent with what was already known, with nausea and vomiting as the most common treatment-related side effects.
The broader safety picture changed in 2025. After deaths from acute liver failure, including in boys who could no longer walk, the FDA updated the Elevidys label in November 2025:
A boxed warning now covers acute serious liver injury and acute liver failure, including fatal cases.
The indication was narrowed to ambulatory patients aged 4 and older. The non-ambulatory indication was removed.
Patients need weekly liver tests for at least three months and weekly troponin-I tests for one month after infusion, along with corticosteroids before and after treatment.
The liver injury is thought to stem from the body's immune response to the very high vector dose needed to reach muscle throughout the body. This remains the central safety challenge for systemic AAV gene therapy. Gene Tech Times covered the start of these safety concerns in Sarepta Pauses Elevidys Gene Therapy Trial After Second Death.
What happens next
Sarepta's EXPEDITION study is following boys from EMBARK over the long term. Of the 64 boys treated in EMBARK Part 1, 52 remain enrolled three years after dosing. Those results, together with the new data in older boys, will shape how doctors and families weigh the benefits against the liver risk.
"Long-term functional outcomes remain the most meaningful way to understand the impact of treatment," Dr. McDonald said.
For families, the practical point is that Elevidys is approved only for boys who can still walk, and these data suggest that treated boys aged 8 to 12 may keep more function than expected. Each decision still depends on a careful conversation with a neuromuscular specialist about liver risk and monitoring. For a clear primer on how AAV vectors carry genes into the body, see my book The Life-Changing Power of Gene Therapy.
The bottom line
Two years after a single infusion, boys with Duchenne who received Elevidys between ages 8 and 12 scored better on three motor tests than matched untreated boys. The evidence comes from an external comparison rather than a randomized trial, and the therapy carries a boxed warning for liver failure, but the data support a benefit in the age group where decline usually accelerates.
Watch the 30-second Short
Watch on YouTube: Duchenne gene therapy: 2-year data in older boys
Keep exploring with Gene Tech Times
Free guide: subscribe to the Gene Tech Times Briefing on our homepage and get Every FDA-Approved Gene Therapy at a Glance in your inbox.
Watch: 30-second gene therapy Shorts on Gene Tech Times Academy.
Read: The Cheat Codes of Our Genes, real stories of mutations that make some people immune to disease.
New to gene therapy? Start with The Life-Changing Power of Gene Therapy.
As an Amazon Associate, Gene Tech Times earns from qualifying purchases.
— T.N., Gene Tech Times
Comments