Effect Sizes of Once-Daily Valbenazine for Tardive Dyskinesia and Chorea Associated with Huntington’s Disease: A Post-Hoc Analysis of Phase 3 Data and Magnitude of Effect

Cohen’s d effect sizes, which describe standardized differences between two means (e.g., mean score changes for placebo and active drug in a clinical trial), are used to compare effects across studies and can be interpreted as small (~0.2), medium (~0.5), or large (~0.8). Once-daily valbenazine is approved for tardive dyskinesia (TD) and chorea associated with Huntington’s disease (HD). Cohen’s d for valbenazine in TD was calculated using data from KINECT® 3 (NCT02274558), a 6-week, fixed-dose study (valbenazine 40 or 80 mg) with efficacy assessed based on change from baseline (CFB) in the Abnormal Involuntary Movement Scale (AIMS) total score. Least-squares mean differences (LSMDs) between treatment groups at Wk6 (end of double-blind treatment) indicated greater AIMS CFB with valbenazine versus placebo for 80 mg (-3.1, P < 0.0001 [primary endpoint]) and 40 mg (-1.8, nominal P=0.0021 [per fixed-sequence testing]). Valbenazine 80 mg demonstrated a medium effect (d=0.5) as early as Wk2 which increased to a large effect (d=0.9) by Wk6. With valbenazine 40 mg, the effect size increased from d=0.4 (Wk2) to d=0.5 (Wk6). Similar results based on the Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score were found in KINECT®-HD (NCT04102579). Valbenazine effect size increased from Wk2 (d=0.5), with all participants taking the initial 40-mg dose, to Wk10/12 (“maintenance period”) (d=0.9), with 81.8% taking the target 80-mg dose at Wk12 (end of double-blind treatment). These effect sizes based on data from two phase 3 trials demonstrate early and meaningful treatment responses in both TD and HD chorea.