Wave Life Sciences Ltd. has just released positive interim data from the ongoing phase 2 FORWARD-53 study of WVE-N531, an exon skipping oligonucleotide being investigated in boys with Duchenne Muscular Dystrophy (DMD) who are amenable to exon 53 skipping. The interim analysis was conducted after 24 weeks of 10 mg/kg dosing every two weeks, and the results are quite promising.
The key findings include a mean muscle content-adjusted dystrophin expression of 9.0% and unadjusted dystrophin of 5.5%, with high consistency across participants, in a pre-specified analysis. Furthermore, the dystrophin was comprised of two isoforms consistent with Becker Muscular Dystrophy, which displays milder disease. The study also demonstrated meaningful improvement in serum biomarkers for muscle health, with localization of WVE-N531 in myogenic stem cells and regeneration of myofibers.
In terms of safety and tolerability, WVE-N531 was found to be safe and well-tolerated, with treatment-related adverse events being mild and no serious adverse events reported. The data also indicated that WVE-N531 may support monthly dosing going forward, with preclinical data suggesting even higher concentrations in the heart and diaphragm.
The detailed interim results from the FORWARD-53 trial showed that 89% of ambulatory participants achieved muscle content-adjusted dystrophin levels of at least 5%, and the mean exon skipping was 57%. Additionally, participants showed multiple indicators of improvement in muscle health and significant decreases in creatine kinase and aspartate aminotransferase levels, which are serum biomarkers elevated in the presence of muscle damage.
The muscle concentration of WVE-N531 was approximately 41,000 ng/g, with a tissue half-life of 61 days. These results support a monthly dosing regimen for WVE-N531 moving forward.
Wave Life Sciences expects to complete the FORWARD-53 trial and receive feedback from regulators on a pathway to accelerated approval in the first quarter of 2025. The company is also advancing a broader DMD pipeline of oligonucleotides for skipping other exons, with the goal of providing new and best-in-class treatment options for up to 40% of boys with DMD.
This positive interim data has been well-received and has generated considerable interest in the potential of WVE-N531 for the treatment of DMD. The company is also looking ahead to advancing their lead RNA editing and RNAi programs, offering differentiated, best-in-class therapeutic approaches.
Following these announcements, the company's shares moved -6.0%, and are now trading at a price of $5.34. If you want to know more, read the company's complete 8-K report here.
