Wave Life Sciences announced today positive data following 48 weeks of dosing in the FORWARD-53 clinical trial evaluating the investigational molecule WVE-N531 in boys with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping. This 48-week data set represents biopsy data for eight of the eleven boys (all ambulatory) who received a 10 mg/kg dosing of WVE-N531 every other week.
Key Results
- WVE-N531 was safe and well tolerated through 48 weeks of dosing.
- WVE-N531 led to 54% mean exon skipping through 48 weeks of dosing.
- WVE-N531 showed dystrophin expression stabilised between 24 and 48 weeks of dosing, with a mean (average) of 7.8% muscle content-adjusted dystrophin; 88% of boys achieved greater than 5% average dystrophin between 24 and 48 weeks.
Participants showed significant improvements in multiple indicators of muscle health through 48 weeks, indicating a shift towards healthy muscle. These data include:
- A statistically significant decline in the amount of muscle fibrosis (scarring) between 24 and 48 weeks.
- Decreases in markers of inflammation
- A 50% decrease in blood creatine kinase (CK), a biomarker for muscle damage, which occurred on top of a stable corticosteroid regimen.
- Improved organisation and uniformity of muscle fibres in muscle tissue.
The data also showed benefits in multiple functional assessments, including:
- Time-to-Rise (TTR) showed a statistically significant and clinically meaningful 3.8-second difference favouring WVE-N531 compared with natural history. This is the largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks.
- North Star Ambulatory Assessment (NSAA) showed positive trends favouring WVE-N531 relative to natural history (1.2-point improvement; not statistically significant).
Next Steps
All 11 boys in FORWARD-53 have advanced to the extension portion of the study, now receiving monthly doses of WVE-N531.
Wave Life Sciences intends to file a New Drug Application (NDA) in 2026 for accelerated approval of WVE-N531. The NDA filing will be based on all FORWARD-53 data, which will include additional data to support monthly dosing. Furthermore, the company is planning for the global confirmatory trial of WVE-N531, advancing their near-term clinical programs for exons 52, 51, 45 and 44, and expect to submit multiple Clinical Trial Applications (CTAs) for other exon skipping programs in 2026.
FORWARD-53
This is a Phase 1b/2 open-label study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical effects of intravenous (IV) WVE-N531 in patients with Duchenne muscular dystrophy (DMD) who have a documented mutation of the DMD gene that is amenable to exon 53 skipping intervention. This study has 2 parts, Part A and Part B. Both Part A and Part B are now completed. Following completion of Part B, all patients have elected to continue to receive study treatment in an optional open-label extension arm.
WVE-N531
WVE-N531 is an exon skipping oligonucleotide being developed as a disease modifying treatment for boys with Duchenne muscular dystrophy amenable to exon 53 skipping. WVE-N531 was designed using Wave’s best-in-class oligonucleotide chemistry modifications, including PN backbone chemistry. WVE-N531 has received Orphan Drug Designation and Rare Paediatric Disease Designation from the U.S. Food & Drug Administration.
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