Objective:

To assess treatment effect sizes of uniquely selective valbenazine for tardive dyskinesia (TD).

Background:

Valbenazine is approved for TD and chorea associated with Huntington’s disease. 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 treatment 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 have been reported for common neuropsychiatric medications relative to placebo, including antidepressants for major depressive episodes (d=0.4), antipsychotics for schizophrenia (d=0.5), deutetrabenazine for TD (d=0.6), and levodopa for Parkinson’s disease (d=0.9).

Design/Methods:

Cohen’s d effect sizes for valbenazine in TD were calculated using Abnormal Involuntary Movement Scale (AIMS) data from KINECT® 3 (NCT02274558), a 6-week phase 3 study with valbenazine (40 or 80 mg) versus placebo. Effect sizes were calculated at all 3 post-baseline study visits using the difference between valbenazine and placebo for the mean AIMS score change from baseline divided by the pooled standard deviation.

Results:

The least squares mean changes from baseline to Week 6 in AIMS total score were -3.2, -1.9, and -0.1 for valbenazine 80 mg, valbenazine 40 mg, and placebo, respectively. Placebo-corrected improvements (i.e., least squares mean differences [LSMDs] between treatment groups) were -3.1 for 80 mg (P<0.0001 [primary endpoint]) and -1.8 for 40 mg (nominal P=0.0021 [per fixed-sequence testing]). For valbenazine 80 mg, a medium effect (d=0.5) was detected at Week 2,  which increased to a large effect (d=0.9) by Week 6. With valbenazine 40 mg, the effect sizes also increased from Week 2 (d=0.4) to Week 6 (d=0.5).

Conclusions:

Based on AIMS data from KINECT 3, meaningful effect sizes were detected as early as Week 2 with a large effect size noted for valbenazine 80 mg by Week 6.