(59) Indirect treatment comparison for early efficacy of VMAT2 inhibitors for tardive dyskinesia and chorea associated with Huntington’s disease

Background: : Two vesicular monoamine transporter 2 (VMAT2) inhibitors, valbenazine and deutetrabenazine, are approved for the treatment of both tardive dyskinesia (TD) and chorea associated with Huntington’s disease (HD).

Objective: : To compare efficacy early during treatment, two indirect treatment comparison (ITC) analyses of valbenazine versus deutetrabenazine were conducted using data from their respective placebo-controlled studies for TD and HD chorea.

Methods: : For TD, ITC analysis was based on the Abnormal Involuntary Movement Scale (AIMS) total score. Mean AIMS score changes were obtained for valbenazine and placebo from the 6-week KINECT® 3 study, and for deutetrabenazine and placebo from the pooled 12-week AIM-TD and ARM-TD studies. For HD chorea, the Total Maximal Chorea (TMC) score of the Unified Huntington’s Disease Rating Scale (UHDRS®) was the basis for ITC analysis. Mean TMC changes were obtained for valbenazine and placebo from KINECT®-HD and for deutetrabenazine and placebo from FIRST-HD; both studies included 12 weeks of treatment. Using the Bucher method, ITC analyses of valbenazine versus deutetrabenazine for TD and HD chorea were conducted at intermediate Week 2 and Week 4 timepoints.

Results: : For TD, ITC of AIMS total score improvement numerically favored valbenazine at Weeks 2 and 4; differences between valbenazine and deutetrabenazine for placebo-relative AIMS decreases were -0.75 (95% CI: -2.10, 0.60) at Week 2 and -0.96 (95% CI: -2.13, 0.22) at Week 4. For HD chorea, ITC based on TMC score improvement statistically favored valbenazine versus deutetrabenazine, with differences for placebo-corrected TMC decreases of -1.88 (95% CI: -3.23, -0.52) at Week 2 and -1.84 (95% CI: -3.43, -0.25) at Week 4.

Conclusions: : Based on indirect comparisons of relative efficacy, favorable improvements were found with valbenazine versus deutetrabenazine during early treatment for both TD and HD chorea. Magnitude of effect and time needed to reach an effective dose are important considerations when choosing a medication to treat the hyperkinetic movement disorders of TD or HD chorea.

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