Sarepta Reports Three-Year Topline Data from Phase 3 DMD Study

Rare Daily Staff

Sarepta Therapeutics said data from a phase 3 study of its gene therapy Elevidys showed it significantly slowed disease progression over three years in ambulatory boys with the rare neuromuscular disease Duchenne muscular dystrophy.

Boys who received a single infusion of Elevidys in Part 1 of the EMBARK study maintained mean North Star Ambulatory Assessment scores above their baseline three years after treatment, while a pre-specified, propensity‑weighted external control group continued to decline below baseline.

Elevidys-treated patients showed a 73 percent slowing of disease progression on Time to Rise and a 70 percent slowing on the 10‑meter walk/run compared with the external control group, with the treatment effect widening between Year 2 and Year 3.

Topline analyses showed statistically significant and clinically meaningful differences across all three key motor outcomes compared with the external controls. Sarepta said patients treated in Part 1 maintained significantly higher levels of motor function three years after dosing than those in the external control dataset, which pooled participants from one randomized trial and two natural history cohorts matched via propensity score weighting.

Sarepta reported no new treatment‑related safety signals in the three‑year follow‑up, saying the findings are consistent with the previously described manageable safety profile of Elevidys in ambulatory patients.

Duchenne muscular dystrophy is caused by a mutation in the gene that encodes instructions for dystrophin. Symptoms of Duchenne usually appear in infants and toddlers, and affected children may experience developmental delays such as difficulty walking, climbing stairs, or standing from a sitting position.

As the disease progresses, muscle weakness in the lower limbs spreads to the arms and other areas. Most patients require full-time use of a wheelchair in their early teens and then progressively lose the ability to perform activities of daily living independently, such as using the restroom, bathing, and feeding. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilatory support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually die in their 20s.

Elevidys, a single‑dose adeno‑associated virus gene transfer therapy designed to deliver a micro‑dystrophin transgene to skeletal muscle, is currently the only approved gene therapy for Duchenne. Following an FDA label update announced in late 2025, the product is indicated for ambulatory individuals 4 years and older with a confirmed mutation in the DMD gene, and its label includes limitations and safety warnings reflecting liver‑related risks observed in broader use.

The company said analysis of the longer‑term dataset is ongoing, including functional outcomes for patients who received Elevidys after crossover in Part 2, and it plans to present additional results at upcoming medical meetings and in peer‑reviewed publications.

“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,” said Louise Rodino‑Klapac, president of research and development and technical operations at Sarepta. “These statistically significant benefits not only persist but continue to strengthen over time, creating a sustained and growing separation from the expected disease trajectory.”