WVE-N531, an oligonucleotide, elicited significant functional benefit and reversal of muscle damage in the Phase II FORWARD-53 trial. Wave plans to file for accelerated approval of the candidate in 2026.
Wave Life Sciences’ Duchenne muscular dystrophy exon-skipper elicited what the company’s CEO called “unprecedented” results, significantly improving functional benefit and reversing the hallmark muscle damage of the disease in 11 boys in a mid-stage trial.
“Bottom line, [the] data is impressive,” Truist Securities wrote in an investor note Wednesday, citing an improvement in time-to-rise (TTR), reversal of muscle damage and dystrophin expression. Wave’s shares rose 7% as the markets opened to $10.10, from $9.44 at close on Tuesday.
Wave announced 48-week data from the Phase II FORWARD-53 trial of its exon-skipper WVE-N531 on Wednesday. The drug is an oligonucleotide being studied in boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping.
The data, from 11 boys ages 5-11 with DMD—10 ambulatory and one non-ambulatory—showed a 3.8 second difference on the time-to-rise scale versus natural history controls, “the largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks,” according to Wave. Treatment with WVE-N531 also led to a 1.2-point improvement on the North Star Ambulatory Assessment (NSAA), which is a scale used to measure functional motor abilities in ambulant children with Duchenne. Mizuho analysts said this result was not statistically significant, “but a notable trend,” according to a Wednesday note. WVE-N531 also led to a 28.6% reduction in fibrosis, driven by decreases in inflammation and necrosis and “coupled with transition from regenerative to mature muscle,” according to Wave.
On an investor call Wednesday, CEO Paul Bolno called the overall data “unprecedented” and emphasized this result, saying, “This is the first time that a significant reversal in muscle fibrosis has been observed,” with an exon-skipping therapy.
Dystrophin expression—a key biomarker in DMD, which is caused by a mutation in the gene for the dystrophin protein—stabilized between 24 and 48 weeks, the biotech reported, averaging 7.8%, with 88% of boys achieving greater than 5% average dystrophin.
WVE-N531 was safe and well-tolerated, with no serious adverse events, according to Wave.
These results come amid a busy March for the DMD space. Last week, several companies—including Dyne Therapeutics, REGENXBIO and Genethon—presented new data for their candidates at the 2025 Clinical & Scientific Conference of the Muscular Dystrophy Association in Dallas, with both Dyne and REGENXBIO on track for regulatory submissions next year.
Wave, too, intends to file for accelerated approval of WVE-N531 in 2026, following FDA feedback, according to Wednesday’s press release.
Wave’s results may also be a balm for the DMD community after the revelation last week that a teenage patient taking Sarepta’s approved gene therapy Elevidys had died. The death was linked to acute liver failure, according to Sarepta, which added that a cytomegalovirus (CMV) infection was “a possible contributing factor” to the death.
The DMD space has seen significant progress in the past decade, capped by the 2023 approval of Elevidys as the first gene therapy for the disease.
However, “Despite progress in Duchenne, there remains a significant unmet need for therapeutics that meaningfully impact disease progression,” Pat Furlong, founder and president of Parent Project Muscular Dystrophy, said in a statement Wednesday. “Paired with monthly administration and a continued favorable safety profile, WVE-N531 represents a significant step forward – not just for individuals amenable to exon 53 skipping, but also for the broader exon skipping field.”
