Deutetrabenazine Effect on Total Motor Score in Patients with Huntington Disease (First-HD) (S27.008)

OBJECTIVE: To quantify deutetrabenazine changes in overall motor measures, as assessed by the Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score (TMS). BACKGROUND: Huntington disease (HD) is a hereditary, progressive, neurodegenerative disorder characterized by chorea, cognitive dysfunction and psychiatric symptoms. Deutetrabenazine (SD-809) is a novel molecule currently under development for treatment of HD associated chorea. DESIGN/METHODS: 90 subjects were randomized (1:1) to treatment with deutetrabenazine or placebo in this double-blind, placebo-controlled, parallel-group study. Enrolled subjects were ambulatory adults diagnosed with motor manifest HD, as indicated by motor exam features and an expanded HTT CAG repeat (≥37), and who had a baseline total maximal chorea (TMC) score ≥8. The TMC comprises 7 of the 31 items in the TMS. TMC was the primary endpoint and TMS was a pre-specified endpoint. RESULTS: In the deutetrabenazine group, TMS improved from baseline by 7.4 points (standard error [SE] 0.9) versus 3.4 points (SE 0.9) in the placebo group (P=0.002). This result was driven by significant improvements in chorea (primary endpoint; improved by 4.4 versus 1.9 points, P<0.0001) and dystonia (improved by 0.9 versus 0.1 points, P=0.02). Changes in other UHDRS motor components did not differ significantly between treatment groups, and there was no worsening in gait or parkinsonism subscores. Rates of depression, irritability, insomnia were low and similar to or less than those observed with placebo. CONCLUSION: While deutetrabenazine clearly improved chorea, there was also significant improvement in TMS, with substantial contributions from improved dystonia. Combined with its favorable safety profile, the TMS findings suggest deutetrabenazine can provide clinically meaningful overall motor benefit to patients with HD. Study Supported by: Auspex Pharmaceuticals - a wholly owned subsidiary of Teva Pharmaceuticals, Inc. Disclosure: Dr. Frank has received research support through the Huntington Study Group, funded by Auspex Pharmaceuticals. Dr. Stamler has received personal compensation for activities with Auspex Pharma as an employee. Dr. Sung has received personal compensation for activities with Auspex Pharmaceuticals and Lundbeck, Inc. as a consultant. Dr. Claassen has received research support from Auspex Pharmaceuticals. Dr. Janicki has nothing to disclose. Dr. Loy has nothing to disclose. Dr. Furr-Stimming has nothing to disclose. Dr. Oakes has received personal compensation in an editorial capacity for Springer. Dr. Testa has received research support from the Huntington Study Group Ltd.