Category: Huntington's Disease
Objective: To present safety and efficacy results from a long-term study of once-daily valbenazine for chorea associated with Huntington’s disease (HD).
Background: In a 12-week phase 3 trial (KINECT®-HD [KHD]), HD chorea significantly improved with valbenazine versus placebo. Participants from this study, along with eligible individuals who did not participate in KHD, were included in KINECT®-HD2 (NCT04400331), an open-label study that evaluated the long-term safety and tolerability of valbenazine and its maintenance of effect on chorea. An optional extended-maintenance period is ongoing.
Method: Participants received valbenazine (≤80 mg, once-daily) for ≤156 weeks. Treatment-emergent adverse events (TEAEs) were monitored throughout the study, including serious TEAEs (per investigator judgment) and treatment/study discontinuation due to a TEAE. Efficacy, analyzed descriptively, included mean change from baseline (BL) for the UHDRS® Total Maximal Chorea (TMC) score and response status (“much improved” or better) for the Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C).
Results: Of the 154 participants who received ≥1 valbenazine dose, 150 (97.4%) had ≥1 TEAE; the most common TEAEs were falls (42.9%), somnolence (25.3%), and fatigue (21.4%). No single TEAE was judged as serious in ≥2% of participants; no TEAE led to discontinuation in ≥3% of participants. At BL, the mean (±SD) TMC score was 12.0±3.5 (n=154). Mean TMC score changes from BL (±SEM) were as follows: week 2 (first post-BL visit after initial VBZ 40 mg dose, -3.4±0.3 [n=146]); week 104 (2 years, ‑5.2±0.5 [n=87]); and week 156 (3 years, -2.9±1.2 [n=18]). PGI-C response status results were as follows: week 2 (34.5% [50/145]); week 104 (75.9% [66/87]); and week 156 (77.8% [14/18]). Similar results were found for CGI-C. Sixty-six (42.9%) active participants had not reached the week 156 visit when the extended-maintenance period was initiated.
Conclusion: KINECT-HD2 demonstrated long-term safety and tolerability of once-daily valbenazine. TEAEs were consistent with symptoms common to HD and/or adverse events reported in previous clinical trials of VMAT2 inhibitors for HD chorea. Chorea improvements were observed early with valbenazine and sustained through three years of treatment.
To cite this abstract in AMA style:
E. Furr Stimming, E. Kayson, S. Karpuram, J. Goldstein, S. Hinton, O. Klepitskaya, H. Zhang, E. Dunayevich, D. Haubenberger. Long-Term Safety and Efficacy of Valbenazine for Treating Huntington’s Disease Chorea [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/long-term-safety-and-efficacy-of-valbenazine-for-treating-huntingtons-disease-chorea/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-safety-and-efficacy-of-valbenazine-for-treating-huntingtons-disease-chorea/