Objective: To present interim analyses from KINECT®-HD2 (NCT04400331), an ongoing open-label study of once-daily valbenazine (VBZ) for chorea associated with Huntington’s disease (HD).

Background: In the Phase 3 KINECT®-HD study (NCT04102579), VBZ significantly improved chorea versus placebo in adults with HD. Concomitant antipsychotics are allowed in KINECT-HD2, which was designed to evaluate the long-term safety of VBZ and its maintenance of effect on chorea.

Method: KINECT-HD2 participants received once-daily VBZ (starting dose: 40 mg; target maintenance dose: 80 mg) for up to 156 weeks with an optional 2-year extension. Efficacy outcomes up to Wk50 (~1 year) from a pre-planned interim analysis are reported. These 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 a subgroup already receiving stable antipsychotic treatment at enrollment is also presented, along with treatment-emergent adverse events (TEAEs) for all participants. All outcomes are presented descriptively.

Results: At the time of the pre-planned interim analysis, 125 participants had received ≥1 VBZ dose. Mean (±SD) TMC score was 11.9±3.5 at baseline. TMC improvements were observed by Wk2 at the initial VBZ dose of 40 mg (‑3.4±3.1 [n=118]) and sustained from Wk8 (‑5.6±3.6 [n=110]) to Wk50 (-5.8±4.1 [n=66]) at doses up to 80 mg. In participants already receiving antipsychotic treatment, similar improvements in TMC score 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. Of the 125 participants in the pre-planned analysis, 119 (95.2%) reported ≥1 TEAE and 17 (13.6%) discontinued due to a TEAE. The most common TEAEs were falls (30.4%), fatigue (24.0%), and somnolence (24.0%). TEAEs in most participants were moderate (40.8%) or mild (44.0%).

Conclusion: In addition to supporting findings from KINECT-HD, pre-planned interim results from KINECT-HD2 suggest that once-daily VBZ may provide sustained clinically meaningful chorea improvement for up to ~1 year, with an acceptable safety and tolerability profile. Preliminary analyses indicate the clinical profile of VBZ is similar irrespective of background antipsychotic therapy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sustained-chorea-improvements-with-long-term-once-daily-valbenazine-in-adults-with-huntingtons-disease/