Wave Life Sciences Ltd. has just released positive data from the phase 2 FORWARD-53 clinical trial of WVE-N531, an exon skipping oligonucleotide being investigated in boys with Duchenne Muscular Dystrophy (DMD) amenable to exon 53 skipping. The trial demonstrated significant functional benefits and a reversal of muscle damage after 48 weeks of dosing with WVE-N531. Here are the key findings:
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Time-to-rise (TTR) data showed a statistically significant and clinically meaningful improvement of 3.8 seconds versus natural history at 48 weeks, representing the largest effect observed relative to any approved dystrophin restoration therapy at that timepoint.
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Dystrophin expression stabilized between 24 and 48 weeks and averaged 7.8%, with 88% of boys achieving greater than 5% average dystrophin between these time periods.
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The trial also showed a statistically significant reduction in fibrosis, coupled with a transition from regenerative to mature muscle, driven by decreases in inflammation and necrosis.
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WVE-N531 was found to be safe and well-tolerated, with no serious adverse events reported.
Following recent feedback from the FDA, Wave intends to file a new drug application in 2026 for accelerated approval, with data to support monthly dosing at launch. Additionally, Wave plans to file Clinical Trial Applications (CTAs) in 2026 for multiple DMD candidates for other exons, with preclinical data supporting a best-in-class exon skipping franchise.
The company also announced that it has met with the U.S. Food and Drug Administration (FDA) on WVE-N531 and intends to file a new drug application (NDA) in 2026 for accelerated approval based on the trial data, which will include additional data to support monthly dosing. The FDA confirmed that the accelerated approval pathway using dystrophin expression as a surrogate endpoint remains open.
Wave expects WVE-N531 to become the first-line treatment of choice for boys amenable to exon 53 skipping, including the 40-50% in the US who are not being treated with approved exon skippers due in part to the burden of weekly infusions coupled with limited efficacy.
In addition to WVE-N531, Wave's programs for exons 52, 51, 45, and 44 leverage best-in-class oligonucleotide chemistry, addressing approximately 40% of the DMD population and representing a >$2.4 billion total market opportunity in the United States alone.
The company also highlighted upcoming milestones across its clinical pipeline of RNA medicines in 2025, including WVE-006 for alpha-1 antitrypsin deficiency, WVE-007 for obesity, and WVE-003 for Huntington’s disease.
These results mark a significant step forward in the development of WVE-N531 and the broader exon skipping field, offering promising hope for individuals with DMD and their families. Following these announcements, the company's shares moved 4.7%, and are now trading at a price of $9.88. For more information, read the company's full 8-K submission here.
