Indirect Treatment Comparison for Early Efficacy of VMAT2 Inhibitors for Tardive Dyskinesia and Chorea Associated with Huntington's Disease
Author(s)
Saurabh Aggarwal, PhD1, Michael Serbin, MBA, MS, PharmD2, Morgan Bron, MS, PharmD2.
1Novel Health Strategies, Chevy Chase, MD, USA, 2Neurocrine Biosciences, Inc., San Diego, CA, USA.
1Novel Health Strategies, Chevy Chase, MD, USA, 2Neurocrine Biosciences, Inc., San Diego, CA, USA.
OBJECTIVES: Two vesicular monoamine transporter 2 (VMAT2) inhibitors, valbenazine and deutetrabenazine, are approved for both tardive dyskinesia (TD) and chorea associated with Huntington’s disease (HD). To compare efficacy early during treatment, two indirect treatment comparison (ITC) analyses of valbenazine versus deutetrabenazine were conducted using data from their 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 Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score 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 both timepoints; 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: 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.
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 Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score 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 both timepoints; 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: 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.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO113
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Neurological Disorders