Objective: To evaluate the sustained safety and efficacy following overnight switch from tetrabenazine (TBZ) to deutetrabenazine in patients with chorea associated with Huntington disease (HD).

Background: The only FDA-approved treatment for HD, TBZ, has shown chorea control, but dose-related tolerability concerns exist. Deutetrabenazine is a novel molecule containing deuterium, a naturally occurring, nontoxic form of hydrogen that extends active metabolite half-lives, enabling the use of lower dose and frequency to achieve efficacy. Improved motor function after overnight switch to deutetrabenazine at Week 8 was reported previously; here, we report updated data for the entire switch cohort through Week 8.

Methods: HD patients on a stable TBZ regimen were enrolled in this open-label, single-arm study. Treatment was switched overnight to a deutetrabenazine dose predicted to yield comparable daily exposure to active metabolites. Dose could be adjusted for optimal chorea control up to Week 8. Changes in total maximal chorea (TMC) and total motor score (TMS) from baseline (BL) were efficacy measures. Adverse events (AEs) were monitored throughout the study.

Results: Of 37 enrolled patients, 36 completed 8 weeks of treatment. Deutetrabenazine significantly reduced mean [SD] TMC score from BL at Week 8 (-2.06 [3.25], P=.0006). The mean [SD] TMS decreased from BL at Week 8 (-2.43 [8.68], P=.1018). Twenty (54.1%) deutetrabenazine patients reported treatment-emergent AEs, in 14 of whom the AEs were considered treatment related. Neuropsychiatric AEs were uncommon: anxiety and depression were each reported in 2 (5.4 %) subjects. There were low rates of dose reductions/suspensions, no study withdrawals due to AEs, and no deaths reported through Week 8.

Conclusions: Deutetrabenazine significantly improved chorea measured by TMC at Week 8 and had a favorable safety profile, supporting that overnight switch from TBZ to deutetrabenazine can safely maintain clinical outcomes. References: 1. Huntington Study Group. Neurology 2006;66:366-372. 2. Huntington Study Group. Alternatives for Reducing Chorea in Huntington Disease (ARC-HD). Presented at International Congress of Parkinson’s disease and Movement Disorders; June 18, 2015; San Diego, CA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alternatives-for-reducing-chorea-in-huntington-disease-a-long-term-trial-arc-hd-updated-week-8-results-for-the-switch-cohort/