Wave Life Sciences (WVE) Study Result summary

Study background and objectives

• FORWARD-53 is an open-label, phase 2 study evaluating WVE-N531 in boys with DMD amenable to Exon 53 skipping, aiming to restore dystrophin expression and improve muscle health.

• The study enrolled 11 boys aged 5–11, all on stable steroids, with 10 ambulatory and 1 non-ambulatory participant.

• WVE-N531 targets 8–10% of DMD cases, with potential to address up to 40% with additional exon skipping therapies.

• The therapeutic goal is to achieve consistent dystrophin expression of at least 5% of normal, associated with milder disease phenotypes.

• Key endpoints include safety, tolerability, pharmacokinetics, pharmacodynamics, and functional measures at 24 and 48 weeks.

Interim results and efficacy

• Mean muscle content-adjusted dystrophin reached 9% (5.5% unadjusted), with 89% of ambulatory boys achieving at least 5%.

• Dystrophin produced was comprised of two isoforms consistent with Becker muscular dystrophy, indicating a milder disease profile.

• High exon skipping (mean 57%) confirmed restoration of the dystrophin reading frame.

• WVE-N531 demonstrated high muscle tissue concentrations (~41,000 ng/g) and a tissue half-life of 61 days, supporting monthly dosing.

• Significant decreases in serum CK and AST indicated improved muscle health, with reductions larger than typically seen with steroid introduction.

Safety and tolerability

• WVE-N531 was safe and well tolerated, with only mild treatment-related adverse events and no serious events, discontinuations, or oligonucleotide class effects.

• 90.9% of patients experienced at least one treatment-emergent adverse event, but none were severe or led to discontinuation.

• The safety profile is described as extraordinarily clean for an exon-skipping therapy.