Wave Life Sciences Ltd. has announced positive results from its phase 1b/2a Select-HD clinical trial of WVE-003, a potential disease-modifying therapeutic for Huntington’s disease (HD). In the multidose portion of the trial, participants who received every-eight-week intrathecal doses of 30 mg WVE-003 demonstrated several key outcomes compared to the placebo group:
- WVE-003 was generally safe and well-tolerated, with no serious adverse events reported.
- Significant mutant huntingtin (mhtt) protein lowering was observed throughout the 28-week assessment period.
- At 24 weeks, mean mhtt lowering in cerebrospinal fluid (CSF) was 46% versus placebo (p=0.0007), and at 28 weeks, it was 44% versus placebo (p=0.0002), supporting quarterly or less frequent dosing.
- Wild-type huntingtin (wthtt) protein was preserved throughout the assessment period, with statistically significant increases observed versus placebo. This protein is crucial for neuronal function and CSF flow in the ventricles.
- Most WVE-003-treated participants had neurofilament light protein (nfl) levels in the range of placebo or had nfl levels that increased and returned to the range of placebo.
- At 24 weeks, mhtt reduction was correlated with slowing of caudate atrophy (r=-0.50; p=0.047), an imaging biomarker predictive of clinical outcomes.
The company plans to engage regulators on a clinical development path that could support potential accelerated approval for WVE-003 and will submit its opt-in package to program partner Takeda. These results mark the first-ever clinical demonstration of allele-selective silencing in any disease target, and Wave Life Sciences expects its current cash and cash equivalents to fund operations into the fourth quarter of 2025.
The company will host an investor conference call and webcast to discuss the Select-HD clinical trial results.
Today the company's shares have moved -10.0% to a price of $4.69. Check out the company's full 8-K submission here.
