Objective: To evaluate the effects of valbenazine (VBZ) on mobility, abnormal movements, and hand/arm function as assessed using the Huntington’s Disease Health Index (HD-HI).

Background: Over 90% of individuals with Huntington’s disease (HD) will develop chorea, which contributes to imbalance, falls, poor coordination, and impaired dexterity. Once-daily VBZ was approved for chorea associated with HD based on results from KINECT®-HD (K-HD: NCT04102579). In this 12-week phase 3 trial, HD chorea improved significantly with VBZ versus placebo (PBO), as indicated by changes from the baseline period (average of screening and baseline scores) to the maintenance period (average of Week 10 and Week 12 scores) in the UHDRS® Total Maximal Chorea score. K-HD was also first phase 3 trial to implement the HD-HI, a disease-specific patient-reported assessment developed with patients and caregivers, as an exploratory endpoint.

Method: Post-hoc analyses were conducted in motor-related HD-HI subscales: mobility/ambulation (14 items); abnormal movements (7 items); and hand/arm function (9 items). Mean changes from baseline to maintenance (Wk10/12) were analyzed in “affected” participants, defined as having a baseline item score ≥2 (affected “a little” to “severely”). Statistical testing was performed post hoc, with no adjustments for multiple comparisons and without inferential intent; thus, all P-values are considered nominal.

Results: Of the 30 items across the motor-related HD-HI subscales, 29 had a numerically superior improvement with VBZ versus PBO at Wk10/12. For mobility/ambulation, statistically significant improvements were found in 1 item: limitations with mobility or walking (-0.93 vs -0.19 for PBO, P=0.004). For abnormal movements, significant improvements were found in 3 items: abnormal movements (-1.52 vs -0.78, P=0.006); impaired coordination (-0.95 vs -0.35, P=0.047); and hard time sitting still (-1.64 vs -0.86, P=0.022). For hand/arm function, significance was found for 1 item: problems knocking things over (-0.97 vs -0.38, P=0.040).

Conclusion: Based on patient self-reports, VBZ was associated with greater improvements in mobility, abnormal movements, and hand/arm function compared to PBO over the 12-week K-HD trial. These findings suggest that the effect of VBZ to reduce HD chorea may also decrease disease burden in motor-related domains.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/decreased-disease-burden-in-motor-related-hd-hi-domains-among-adults-with-huntingtons-disease-treated-with-valbenazine/