Sustained Improvements with Once-daily Valbenazine in Chorea Associated with Huntington’s Disease: Interim Results from a Long-term Open-label Study
Erin Furr Stimming1, Daniel Claassen2, Elise Kayson3, Jody Goldstein3, Sean Hinton4, Olga Klepitskaya4, Hui Zhang4, Grace Liang4, Dietrich Haubenberger4
1The University of Texas Health Science Center at Houston, McGovern Medical School, 2Vanderbilt University Medical Center, 3Huntington Study Group®, 4Neurocrine Biosciences, Inc.
Objective:
To present interim analyses from KINECT®-HD2 (NCT04400331), an ongoing open-label study of once-daily valbenazine for chorea associated with Huntington's disease (HD).
Background:
Valbenazine significantly improved chorea versus placebo in KINECT®-HD (NCT04102579). However, more "real-world" data are needed on maintenance of efficacy, long-term tolerability, and effects on chorea when taken with other HD medications (e.g., antipsychotics).
Design/Methods:
KINECT-HD2 participants (including KINECT-HD completers) receive once-daily valbenazine for up to 156 weeks (starting dose: 40mg; target maintenance dose: 80mg). Interim analyses with results up to Wk50 include mean changes from baseline in Unified Huntington’s Disease Rating Scale Total Maximal Chorea (TMC) score and response status (“much improved” or better) for Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C). A preliminary analysis of TMC data from participants already receiving stable antipsychotic treatment at enrollment is also presented, along with treatment-emergent adverse events (TEAEs) for all participants who took ≥1 valbenazine dose. All outcomes were analyzed descriptively.
Results:
127 participants were enrolled at time of analysis. Mean TMC score reductions (±SEM) were observed with valbenazine 40mg by Wk2 (-3.4±0.3, n=118) and sustained with valbenazine ≤80mg from Wk8 (‑5.6±0.3, n=110) to Wk50 (-5.8±0.5, n=66), the last visit retaining >50% of participants. In participants on stable antipsychotic treatment at enrollment, similar improvements were found from Wk4 (-6.0±1.3, n=5) to Wk20 (-5.2±2.2, n=5), the last visit with >2 participants taking concomitant antipsychotics. Response status at Wk50 was 76.9% (50/65) for CGI-C and 74.2% (49/66) for PGI-C. Among 125 participants receiving treatment, 17 (13.6%) reported serious TEAEs, and 17 (13.6%) discontinued due to a TEAE. The most common TEAEs were fall (30.4%, n=38), fatigue (24.0%, n=30), and somnolence (24.0%, n=30).
Conclusions:
In these interim analyses of KINECT-HD2, long-term treatment with once-daily valbenazine was well tolerated and provided clinically meaningful improvement in chorea severity, regardless of concomitant antipsychotic therapy.