Wave Life Sciences (WVE) Study Result summary

Study background and objectives

• SELECT-HD evaluated WVE-003, an allele-selective antisense oligonucleotide, as a disease-modifying therapy for Huntington's disease, targeting mutant huntingtin protein while preserving wild-type protein.

• The study was a global, randomized, double-blind, placebo-controlled Phase 1b/2a trial in HD patients with SNP3, designed to demonstrate safety, pharmacokinetics, potent and selective mutant huntingtin reduction, and preservation of wild-type huntingtin.

• Exploratory endpoints included imaging biomarkers (caudate atrophy) and clinical measures (Total Motor Score, TMS, TFC, SDMT, Stroop, CUHDRS).

Patient population and trial design

• Participants were adults aged 25–60 with HD and SNP3, with balanced baseline characteristics across cohorts.

• The study included single-ascending and multidose phases, with doses of 30, 60, and 90 mg, and dose optimization based on early indicators of target engagement and safety.

Key results and findings

• WVE-003 achieved up to 46% reduction in mutant huntingtin in CSF after three doses, exceeding the 30% threshold expected for clinical impact, with 44% reduction at 12 weeks post last dose (p=0.0002).

• Wild-type huntingtin was preserved or increased, confirming allele selectivity and indicating neuroprotection.

• Multi-dosing was generally safe and well tolerated, with most adverse events mild or moderate and no serious treatment-related AEs in multidose cohorts.

• Most treated participants had neurofilament light protein (NfL) levels similar to placebo or returned to placebo range.

• Ventricular volume remained consistent with natural history, with no hydrocephalus observed.