SELECT-HD (NCT05032196) is an adaptive trial designed to rapidly optimize dose level and frequency based on early indicators of target engagement. The trial update announced today is being driven by the observation of reductions of mutant huntingtin (mHTT) protein in cerebrospinal fluid (CSF) after study participants received either a single 30 or 60 mg dose of WVE-003. Additionally, wild-type huntingtin (wtHTT) protein was preserved, which appears consistent with allele-selectivity.
Key observations include:
- Single doses of WVE-003 up to 90 mg appeared generally safe and well-tolerated and no serious adverse events (SAEs) were observed
- Among participants in the 30 and 60 mg WVE-003 cohorts, the mean reduction in CSF mHTT from baseline was 22% (median reduction 30%) at 85 days following a single dose
- In the 30 and 60 mg cohorts, wtHTT protein was preserved, which appears consistent with allele-selectivity
- Increases in neurofilament light chain (NfL) from baseline were observed in some patients. Wave will continue to monitor trends in NfL as SELECT-HD advances
- There were no clinically meaningful elevations in CSF white blood cell counts or protein that would indicate inflammation in the CNS
- There were no meaningful changes in clinical outcome measures, although the dataset and duration were not sufficient to assess clinical effects
Based on these data, Wave is adapting the SELECT-HD clinical trial to expand the single dose cohorts and will also continue advancing the 90 mg cohort for biomarker analysis at day 85. Additional single dose biomarker and safety data are expected in the first half of 2023.
We are encouraged to see a mean mHTT reduction from baseline of 22% at day 85 after participants received just a single dose of WVE-003, demonstrating a compelling pharmacological profile for individuals with HD. We are grateful to the HD community, including the SELECT-HD participants, study sites, and advisors, for their continued partnership and support of this program. We look forward to continuing to expand this study and sharing additional data next year.
For additional details, here is the link to the full press release.