Objective: To assess the treatment effect size of once-daily valbenazine for tardive dyskinesia (TD) and for chorea associated with Huntington’s disease (HD) using data from two phase 3 clinical trials, KINECT®-3 (NCT02274558) and KINECT®-HD (NCT04102579).

Background: Valbenazine is approved for TD and for chorea associated with HD. The Abnormal Involuntary Movement Scale (AIMS) total score was used in KINECT-3 to assess TD, while the Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score was used in KINECT-HD to assess chorea.

Method: KINECT-3 participants received valbenazine (40 or 80 mg, fixed dose) or placebo for 6 weeks. The primary endpoint was the least squares (LS) mean change in AIMS total score from baseline to Wk6 for valbenazine 80 mg versus placebo, as assessed by central video raters (movement disorder specialists) who were blinded to both treatment and visit. KINECT-HD participants received valbenazine or placebo for 12 weeks. Valbenazine was initiated at 40 mg, then increased to 60 mg at Wk2 and 80 mg at Wk4, as tolerated; participants were maintained through the rest of the treatment period on their highest tolerated dose (max: 80 mg). The primary endpoint was LS mean change in TMC score from screening/baseline period (average of each participant’s screening and baseline scores) to maintenance period (average of each participant’s Wk10 and Wk12 scores), as assessed by Huntington Study Group site investigators. In both studies, statistical significance was based on the LS mean difference (LSMD) between valbenazine and placebo. Effect sizes (Cohen’s d) were analyzed using the primary endpoint results.

Results: In KINECT-3, LS mean changes from baseline to Wk6 in AIMS total score were greater with valbenazine versus placebo, with LSMDs of -3.1 for 80 mg (P<0.0001) and -1.8 for 40 mg (nominal P=0.0021, per fixed-sequence testing procedure). These results translated to a large effect size with 80 mg (d=0.89) and moderate effect size with 40 mg (d=0.52). In KINECT-HD, TMC improvement from screening/baseline to maintenance was greater with valbenazine versus placebo, with an LSMD of -3.2 (P<0.0001) and large effect size (d=0.93).

Conclusion: This post-hoc analysis of phase 3 clinical trial data indicates strong efficacy with once-daily valbenazine for both TD and for HD-associated chorea.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/treatment-effect-sizes-of-once-daily-valbenazine-for-tardive-dyskinesia-and-for-chorea-associated-with-huntingtons-disease-a-post-hoc-analysis-of-phase-3-clinical-trial-data/