Sustained Chorea Improvements with Long-term, Once-daily Valbenazine in Adults with Huntington’s Disease
Erin Furr Stimming1, Daniel Claassen2, Elise Kayson3, Raja Mehanna1, Shree Karpuram4, Jody Goldstein4, Sean Hinton4, Olga Klepitskaya4, Hui Zhang4, Eduardo Dunayevich4, Grace Liang4, Dietrich Haubenberger4
1The University of Texas Health Science Center at Houston, McGovern Medical School, 2Vanderbilt University Medical Center, 3Huntington Study Group® (at time of study), 4Neurocrine Biosciences, Inc.
Objective:
To present results from KINECT®-HD2 (NCT04400331), an open-label study of once-daily valbenazine for chorea in adults with Huntington's disease (HD).
Background:
In the phase 3 KINECT®-HD (NCT04102579) study, valbenazine significantly improved chorea versus placebo. Concomitant antipsychotics were allowed in KINECT-HD2, which was designed to evaluate long-term safety and tolerability of valbenazine and its maintenance of effect on chorea.
Design/Methods:
KINECT-HD2 participants received once-daily valbenazine (starting dose: 40 mg; target maintenance dose: 80 mg) for ≤156 weeks with an optional 2-year extended-maintenance period. Safety outcomes include treatment-emergent adverse events (TEAEs), as reported at any study visit in the overall study population. Efficacy outcomes are reported through Week 104 and include the following: 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). TMC results are also presented for subgroups taking concomitant antipsychotics through Week 50. Outcomes are presented descriptively.
Results:
Among 154 participants receiving ≥1 dose of valbenazine, 150 (97.4%) reported ≥1 TEAE and 24 (15.6%) discontinued due to a TEAE, most commonly for fatigue (2.6%) and anxiety (2.6%). Common TEAEs were fall (42.9%), somnolence (25.3%), and fatigue (21.4%). Serious TEAEs were reported for 24 (15.6%) participants. Mean (±SEM) TMC improvements were observed by Week 2 with valbenazine 40 mg (‑3.4±0.3 [n=146]) and sustained with ≤80 mg from Week 8 (‑5.7±0.3 [n=139]) to Week 104 (-5.2±0.5 [n=87]). TMC improvements were similar through Week 50 for participants taking concomitant antipsychotics (-6.0±1.1 [n=20]) and for those with no concomitant antipsychotic use (-5.7±0.4 [n=84]).
Conclusions:
KINECT-HD2 results indicate acceptable long-term safety/tolerability of once-daily valbenazine, along with rapid, sustained, and clinically meaningful chorea improvement. Outcomes with valbenazine in adults with HD chorea were unaffected by concomitant use of antipsychotic therapy.
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