Neurocrine Biosciences, Inc. presented subgroup analyses and data from the KINECT®-HD study showing the impact of INGREZZA® (valbenazine) capsules on emotional health and psychiatric stability in patients with chorea associated with Huntington's disease. The subgroup analysis showed consistent efficacy in reducing chorea compared to placebo across all identified subgroups, categorized by demographics and baseline assessment scores. A separate data analysis showed improvements in some aspects of emotional health with no worsening of psychiatric symptoms. This research will be shared at the 2024 Annual Meeting of the Huntington Study Group in Cincinnati.

Efficacy of Valbenazine for Chorea Associated with Huntington's Disease: Subgroup Analyses of KINECT®-HD Results: This analysis was conducted to assess the effects of INGREZZA (n=64) versus placebo (n=61) in subgroups of participants from the Phase 3 KINECT-HD study using the Unified Huntington's Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score. Participants in the study were randomized 1:1 to receive placebo or INGREZZA, with a starting dose of 40 mg that was increased up to 80 mg over an 8-week period as tolerated, for a total treatment period of 12 weeks. In the full analysis set, least-squares mean (LSM) changes for TMC score indicated significantly greater chorea improvements for INGREZZA versus placebo, with an LSM difference at maintenance of -3.2 (95% confidence interval (CI): -4.4 to -2.0; P < 0.0001).

To further assess INGREZZA efficacy, TMC changes were analyzed in subgroups categorized by demographics (sex, age and body mass index) and baseline assessment scores (Clinical Global Impression of Severity, Patient Global Impression of Severity, Anosognosia Scale, UHDRS Total Functional Capacity, UHDRS Total Motor Score and UHDRS TMC). TMC changes favored INGREZZA over placebo in all 19 subgroups, with the LSM difference (LSMD; 95% CI) ranging from -4.5 (-6.6 to -2.4) to -1.6 (-4.1 to 0.8). Results were favorable for INGREZZA in 17 of the 19 subgroups.

The 95% CIs for all subgroup LSMDs encompassed the primary endpoint LSMD of -3.2. Effects of Valbenazine on Emotional Health and Psychiatric Stability in Adults with Huntington's Disease: This separate post hoc analysis of the Phase 3 KINECT-HD study was conducted to evaluate emotional health and psychiatric stability in participants taking INGREZZA (n=64) or placebo (n=61) utilizing the Huntington's Disease Health Index (HD-HI) Emotional Health subscale. Mean score changes from baseline (CFB) to Week 10 and Week 12 were analyzed in "affected" participants (those with a baseline item score of at least 2). Safety assessments included adverse events of special interest (AESIs), the Hospital Anxiety and Depression Scale (HADS) and the Columbia-Suicide Severity Rating Scale (C-SSRS).

Results showed that some aspects of emotional health appeared to improve with INGREZZA in affected participants. The largest score changes with INGREZZA compared to placebo at Week 12 were: Anger: -1.7 (INGREZZA; n=17) versus -0.2 (placebo; n=22); Feeling of being overwhelmed: -1.7 (n=20) versus -0.4 (n=27); Fluctuating mood: -1.5 (n=15) versus -0.4 (n=23); Reduced enjoyment with activities: -1.5 (n=25) versus -0.4 (n=26); Emotional outbursts: -1.5 (n=15) versus -0.6 (n=23); Frustration: -1.3 (n=25) versus -0.4 (n=28); Anxiety: -1.4 (n=25) versus -0.5 (n=30). In the safety population (N=127), 5 participants (3 INGREZZA, 2 placebo) reported AESIs related to depression or suicidal ideation.

HADS and C-SSRS shifts from baseline indicated no worsening in anxiety symptoms, depression symptoms or suicidal ideation with INGREZZA. Additional Neurocrine Biosciences posters presented at the 2024 Annual Meeting of the Huntington Study Group include: Huntington's Disease Health Index (HD-HI) Correlations with Clinical Measures: An Analysis of KINECT®-HD Baseline Data. Somnolence-Related Events Over Time with Valbenazine Treatment for Chorea Associated with Huntington's Disease.

Efficacy of Once-Daily Valbenazine in Adults with Chorea Associated with Huntington's Disease: Effect Size Over Time.