Sustained Improvements in Chorea Associated with Huntington Disease with Once-Daily Valbenazine: Interim Results from a Long-Term Open-Label Study
Authors: Stimming Erin Furr , Claassen Daniel O. , Kayson Elise , Goldstein Jody , Hinton Sean C. , Klepitskaya Olga , Zhang Hui , Liang Grace , Haubenberger Dietrich 
Published: January 2025

Introduction

In a recently published Phase 3 trial (KINECT™-HD; NCT04102579), once-daily treatment with valbenazine significantly improved chorea versus placebo in adults with Huntington disease (HD). Individuals who completed KINECT-HD, along with de novo participants, were allowed to enroll in KINECT™-HD2 (NCT04400331), the first long-term study of once-daily valbenazine for chorea associated with HD. Pre-planned interim analyses from this ongoing study were conducted to evaluate the maintenance of valbenazine’s effect on chorea and its long-term safety in adults with HD.

Methods

All KINECT-HD2 participants start valbenazine at 40 mg with increases to 60 mg (Week 2) and 80 mg (Week 4); target maintenance dose is 80 mg once daily until end of treatment (up to 156 weeks). Concomitant antipsychotic medications are allowed. Efficacy outcomes, analyzed by study visit, include mean changes from baseline in Unified Huntington’s Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score and response status for Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C). Responders are defined as participants with a score ≤2 (rating of “much improved” or better). Efficacy outcomes up to Week 50 (˜1 year) are reported. Treatment-emergent adverse events (TEAEs) are presented for all participants who received ≥1 dose of study drug, regardless of time in study (2 to 104 weeks). All interim outcomes were analyzed descriptively.

Results

Of 127 participants enrolled at the time of analysis, 98 (77.2%) had completed KINECT-HD and 29 (22.8%) were newly enrolled. Of 125 participants who received treatment, 65 (52.0%) were female and 118 (94.4%) were white; mean age (±SD) was 54.8 (±11.5) years. A mean reduction in TMC score was observed by Week 2 with valbenazine 40 mg (-3.4 [±3.1], n=118); mean reductions were sustained from Week 8 (5.6 [±3.6], n=110) to Week 50 (-5.8 [±4.1], n=66) (all valbenazine doses). At Week 50, 76.9% (50/65) of participants met the pre-defined threshold for CGI-C response; 74.2% (49/66) met the threshold for PGI-C response. Analyses in participants taking concomitant antipsychotic medications are ongoing and will be presented at the meeting. Of the 125 participants who received treatment, 119 (95.2%) reported at least 1 TEAE and 17 (13.6%) discontinued due to a TEAE. The most commonly reported TEAEs were falls (30.4%), fatigue (24.0%), and somnolence (24.0%).

Conclusions

Interim TMC data from KINECT-HD2 indicated chorea improvement with once-daily valbenazine by Week 2 (3.4 [±3.1] with 40 mg), similar to KINECT-HD Week 2 results (-2.9 [±3.0]). The interim analyses also indicated that long-term treatment with valbenazine was well tolerated and provided clinically meaningful improvement in chorea severity for up to ˜1 year.

Funding

Neurocrine Biosciences, Inc.