Wave Life Sciences’ Phase II open-label trial investigating its disease-modifying drug for boys living with Duchenne Muscular Dystrophy (DMD), WVE-N531, has met all trial endpoints, showing the drug led to significant improvements in muscle health.
Results from the Forward-53 trial (NCT04906460) show the exon-skipping oligonucleotide-based therapy improved muscle health by the end of week 48 including a decline in necrosis and inflammation.
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The trial recruited 11 boys, between the ages of five and 11, amenable to exon 53 skipping only one of whom was non-ambulatory. Typically, DMD develops due to a lack of the protein dystrophin, which helps to protect muscle cells. Results from the Phase II trial saw dystrophin expression stabilised between 24 and 48 weeks, averaging a 7.8% increase.
At the same time, results saw a 50% decrease in serum creatine kinase (CK), an enzyme released into the bloodstream because of muscle damage. Alongside those results, WVE-N531 was able to elicit a 3.8-second difference in TTR versus a natural history of matched untreated patients, using the North Star Ambulatory Assessment (NSAA) system.
Based on US Food & Drug Administration (FDA) feedback, the company said it is planning a 2026 New Drug Application (NDA) for WVE-N531’s accelerated approval.
Laurent Servais, principal investigator in the Forward-53 trial said: “As a clinician deeply involved in patient care and research in muscle diseases like DMD, I am encouraged by these data for WVE-N531 that show dystrophin restoration and several markers of improved muscle condition.
“To see a clinically meaningful and statistically significant difference in TTR versus natural history in a Phase II study is another encouraging finding. I am looking forward to the continued development of WVE-N531.”
The process of exon skipping involves using small, synthetic DNA molecules called antisense oligonucleotides (AONs) to skip specific sections of DNA, known as exons, during the process of RNA splicing, causing the body to produce more dystrophin. One of the few other therapeutics focused on exon 53 skipping is NS Pharma’s Viltepso.
At present, the market for DMD therapies is largely driven by Sarepta Therapeutic’s Elevidys (delandistrogene moxeparvovec) and Santhera Pharmaceuticals’ Agamree (vamorolone), with research by GlobalData estimating that across the seven major markets (7MM: US, France, Germany, Italy, Spain, the UK, and Japan), DMD treatments are expected to grow from sales of $2.3bn in 2023 to $5.2bn by 2033.
If approved for DMD, WVE-N531 could bring in as much as $243m for Wave Life Sciences by the end of 2030.
GlobalData is the parent company of Clinical Trials Arena.
The announcement follows the Muscular Dystrophy Association (MDA) 2025 Conference in Dallas, Texas, that saw updates from Regenxbio’s Phase I/II Affinity trial, as well as Dyne Therapeutics’ Phase I/II DYNE-251 trial.
