Wave Life Sciences Ltd. announced the initiation of dosing in the Phase 2 FORWARD-53 clinical trial, which is evaluating WVE-N531 as a treatment for boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping. FORWARD-53 is designed to assess functional dystrophin protein at 24 and 48 weeks with every other week dosing of WVE-N531. FORWARD-53 is a potentially registrational, open-label, Phase 2 clinical trial that has enrolled 10 boys with DMD who are amenable to exon 53 skipping.

The trial is powered to evaluate functional, endogenous dystrophin expression following 24 and 48 weeks of every other week, intravenous dosing at 10 mg/kg. The primary endpoint is dystrophin protein levels, and the trial is also evaluating pharmacokinetics, digital and functional endpoints, and safety and tolerability. FORWARD-53 is fully enrolled, and Wave expects to deliver data, including dystrophin expression from muscle biopsies, in 2024.

Wave?s Phase 1b/2a Part A proof-of-concept trial in boys with DMD amenable to exon 53 skipping demonstrated high muscle concentrations of WVE-N531 (mean of 6.1 micromolar or 42 micrograms/gram) and mean exon skipping of 53% (range: 48-62%) at six weeks, after boys received three doses of 10 mg/kg every other week. WVE-N531 appeared safe and well-tolerated, with all treatment-related adverse events being mild. Additionally, at Wave?s R&D Day in September 2023, the company shared an analysis of muscle biopsy data from the Part A proof-of-concept trial indicating that WVE-N531 was present in myogenic stem cells, which are important for potential muscle regeneration.

These are the first clinical data in DMD to demonstrate uptake in myogenic stem cells at the early, six-week timepoint and further support the potential differentiation of WVE-N531 from other therapeutics, including gene therapies.