Effect Sizes of Once-daily Valbenazine for Chorea Associated with Huntington’s Disease: A Post-hoc Analysis of KINECT®-HD Data
Raja Mehanna1, Erin Furr Stimming1, Elise Kayson2, Jody Goldstein3, Olga Klepitskaya3, Sean Hinton3, Hui Zhang3, Eduardo Dunayevich3, Grace Liang3, Dietrich Haubenberger3
1The University of Texas Health Science Center at Houston, McGovern Medical School, 2Huntington Study Group® (at time of study), 3Neurocrine Biosciences, Inc.
Objective:
To assess treatment effect sizes of once-daily valbenazine for chorea associated with Huntington’s disease (HD).
Background:
Once-daily valbenazine is approved for chorea associated with HD and tardive dyskinesia. Cohen’s d effect sizes, which describe standardized differences between two means (e.g., mean score changes between placebo and active drug in a clinical trial), are used to compare the magnitude of effects across studies or therapies and can be interpreted as small (0.2-<0.5), medium (0.5-<0.8), or large (≥0.8). Effect sizes reported for common neurologic treatments include levodopa for Parkinson’s disease (0.9), sumatriptan for migraines (0.8), methylphenidate for attention-deficit/hyperactivity disorder (0.8), and memantine for moderate-to-severe Alzheimer’s disease (0.3 to 0.5).
Design/Methods:
Cohen’s d effect sizes for valbenazine in HD chorea were calculated using Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) data from KINECT®-HD (NCT04102579), a 12-week phase 3 study of valbenazine (≤80 mg) versus placebo. Effect sizes were calculated at all post-baseline study visits and at maintenance (average of Week 10 and Week 12 scores) using the difference between valbenazine and placebo for the mean TMC score change from screening/baseline (average of screening and baseline scores) divided by the pooled standard deviation.
Results:
The least squares mean changes from screening/baseline to maintenance in TMC score were -4.6 and -1.4 for valbenazine and placebo, respectively. The placebo-corrected improvement (i.e., least squares mean difference [LSMD] between treatment groups) was -3.2 (
P<0.0001 [primary endpoint]). The effect size increased from Week 2 (
d=0.5), when all participants were taking the initial 40-mg dose, to a large effect (
d=0.9) at maintenance, with 81.8% taking the target 80-mg dose at Week 12.
Conclusions:
Based on TMC data from KINECT-HD, meaningful effect sizes were detected as early as Week 2 at the initial 40-mg dose. Effect sizes for valbenazine generally increased throughout the 12-week trial to a large effect size at maintenance.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.