Wave’s Duchenne Therapy Has Promising Phase 2 Results

New phase 2 data suggest a novel therapy for Duchenne muscular dystrophy (DMD) can reverse muscle damage and lead to significant functional improvement in patients. The news, announced last week by Wave Life Sciences, is expected to result in a new drug application with the FDA next year.

The data come from the FORWARD-53 trial of WVE-N531, an exon-skipping oligonucleotide designed to treat boys with Duchenne muscular dystrophy who are amenable to exon 53 skipping.

Pat Furlong

“Despite progress in Duchenne, there remains a significant unmet need for therapeutics that meaningfully impact disease progression,” said Pat Furlong, the founder and president of the advocacy group Parent Project Muscular Dystrophy, in a press release. “These data demonstrate a promising continuum from dystrophin restoration to regeneration and maturation of muscle tissue, to functional improvement.”

The ongoing, open-label trial involves 11 boys, ranging in age from 5 to 11. All but one of the participants are ambulatory. Participants in the study were given a 10 mg/kg dose of the therapy every two weeks. At 48 weeks, the company said there were no serious adverse events, and all treatment-related adverse events were mild to moderate in intensity.

Biopsy data were available for eight of the 11 participants. Among those patients, the company said that dystrophin expression stabilized between 24 weeks and 48 weeks, averaging 7.8%. All but one of the participants were above 5% average dystrophin.

Functional assessment data were available for all 11 participants. Investigators reported that participants had a 3.8-second improvement in time-to-rise compared with participants’ natural histories. The minimal clinically significant difference for time-to-rise was 1.4 seconds. The company said this represented a larger effect at 48 weeks than any commercially approved dystrophin restoration therapy.

The company also said the therapy led to substantial improvements in muscle health with exon-skipping, including a significant reduction in fibrosis and a transition from regenerative to mature muscle.

“To see a clinically meaningful and statistically significant difference on time-to-rise versus natural history in a phase 2 study is another encouraging finding,” said Laurent Servais, M.D., Ph.D., of the University of Oxford, in the press release. Servais is the principal investigator on the trial.

Wave said it met with the FDA to share its 24-week interim data. The agency confirmed that the therapy is a candidate for the accelerated approval pathway using dystrophin expression as a surrogate endpoint. The company says with this new data it now plans to seek accelerated approval, with an expected new drug application filing expected in 2026.

Wave said it plans to submit the application with data supporting a monthly dosing schedule. President and chief executive Paul Bolno, M.D., said he expects the dosing schedule to make WVE-N531 an attractive option in the marketplace, if approved.

“We expect WVE-N531 to become the first-line treatment of choice for boys amenable to exon 53 skipping, including the 40% to 50% in the United States who are not being treated with approved exon skippers due in part to the burden of weekly infusions, coupled with limited efficacy,” Bolno said.

WVE-N531 is one of a handful of Duchenne therapies in the company’s pipeline. The company is also working on programs based on exons 51, 52, 45, and 44. Altogether, the company says its products, if approved, would address approximately 40% of the Duchenne muscular dystrophy population. Wave says it plans to submit clinical trial applications for other exon-skipping therapies in 2026.