Sustained Chorea Improvements with Long-Term, Once-Daily Valbenazine in Adults with Huntington’s Disease

Abstract: Background: In the phase 3 KINECT®-HD (NCT04102579) study, valbenazine significantly improved chorea versus placebo in adults with Huntington’s disease (HD). KINECT®-HD2 (NCT04400331) is an ongoing, open-label study evaluating valbenazine’s long-term safety and maintenance of effect on chorea; KINECT-HD2 allows concomitant antipsychotic treatment. Methods: KINECT-HD2 participants receive once-daily valbenazine (starting dose: 40mg; target maintenance dose: 80mg) for ≤156 weeks with an optional 2-year extension. Mean changes from baseline in Unified Huntington’s Disease Rating Scale Total Maximal Chorea (TMC) score are reported to Wk50 from a pre-planned interim analysis. Preliminary TMC data from participants receiving stable antipsychotic treatment at enrollment are presented, along with treatment-emergent adverse events (TEAEs) for all participants. Outcomes are presented descriptively. Results: In 125 participants receiving ≥1 valbenazine dose in the pre-planned analysis, mean (±SEM) TMC improvements were observed by Wk2 with valbenazine 40mg (3.4±0.3 [n=118]) and sustained with doses ≤80mg from Wk8 (5.6±0.3 [n=110]) to Wk50 (-5.8±0.5 [n=66]). In participants receiving antipsychotics, similar TMC improvements were found from Wk4 (-5.5±0.7 [n=10]) through Wk38 (-5.8±2.6 [n=4]). Among the 125 participants, 119 (95.2%) reported ≥1 TEAE. The most common TEAEs were falls (30.4%), fatigue (24.0%), and somnolence (24.0%). TEAEs in most participants were mild (44.0%) or moderate (40.8%); 17 participants (13.6%) discontinued due to a TEAE. Conclusions: Interim KINECT-HD2 results indicate that once-daily valbenazine may provide sustained, clinically meaningful chorea improvement for up to 1 year, with acceptable safety/tolerability. Preliminary data suggest valbenazine’s clinical profile for treating chorea in adults with HD is consistent irrespective of background antipsychotic therapy.Short Description: KINECT®-HD2 is an ongoing, long-term, open-label study of once-daily valbenazine for Huntington’s disease chorea. Pre-planned interim analyses indicate early chorea improvement with valbenazine (within 2 weeks at the lowest dose) followed by sustained improvement through 1 year. Valbenazine’s efficacy results and acceptable safety/tolerability profile support findings from the double-blind, placebo-controlled KINECT®-HD study. Preliminary data suggest the clinical profile of valbenazine in treating chorea in adults with Huntington’s disease is consistent regardless of background antipsychotic use.Name of Sponsoring Organization(s): Neurocrine Biosciences, Inc.