Sustained Improvements in Chorea Associated With Huntington Disease With Once-Daily Valbenazine: Interim Results From a Long-Term Open-Label Study

This work was sponsored by Neurocrine Biosciences, Inc. Background: In KINECT™-HD (NCT04102579), valbenazine significantly improved chorea versus placebo in adults with Huntington disease (HD). Pre-planned interim analyses from KINECT™-HD2 (NCT04400331), an ongoing open-label study, were conducted to evaluate the maintenance of valbenazine effect on chorea and its long-term safety in adults with HD, including KINECT-HD study completers. Methods: Participants receive once-daily valbenazine (starting dose: 40mg; target maintenance dose: 80mg) for up to 156 weeks. Efficacy outcomes include mean changes from baseline in Unified Huntington’s Disease Rating Scale® Total Maximal Chorea (TMC) score and Clinical Global Impression of Change (CGI-C) or Patient Global Impression of Change (PGI-C) response status (“much improved” or better). Efficacy outcomes up to Wk50 are reported. Treatment-emergent adverse events (TEAEs) are presented for all participants who took ≥1 dose of study drug. All interim outcomes were analyzed descriptively. Results: Of 127 participants at time of analysis, 98 were from KINECT-HD. Mean TMC score reductions were observed by Wk2 with valbenazine 40mg (-3.4 [±3.1], n=118) and were sustained with ≤80mg from Wk8 (-5.6 [±3.6], n=110) to Wk50 (-5.8 [±4.1], n=66). At Wk50, 76.9% (50/65) of participants were CGI-C responders and 74.2% (49/66) were PGI-C responders. In 125 participants who received treatment, 119 (95.2%) reported ≥1 TEAE; 17 (13.6%) discontinued due to a TEAE. The most common TEAEs were falls (30.4%), fatigue (24.0%), and somnolence (24.0%). Conclusions: Interim data from the open-label KINECT-HD2 study indicate early and sustained chorea improvement through ~1 year with once-daily valbenazine, shown by TMC score reduction and CGI-C and PGI-C