Valbenazine Decreases Disease Burden in Patients with Chorea Associated with Huntington Disease: Patient-Reported Huntington Disease Health Index (HD-HI) Results From the KINECT-HD Trial
Chad Heatwole1, Erin Furr Stimming2, Daniel Claassen3, Elise Kayson4, Jody Goldstein4, Olga Klepitskaya5, Grace Liang6, Dietrich Haubenberger7
1University of Rochester Medical Center, 2The University of Texas Health Science Center at Houston, McGovern Medical School, 3Vanderbilt University Medical Center, 4Huntington Study Group, 5Neurocrine Biosciences, Inc, 6Neurocrine Biosciences, Inc., 7Neurocrine Biosciences
Objective:
To describe results of the Huntington Disease Health Index (HD-HI) in KINECT-HD (NCT04102579).
Background:
In KINECT-HD, adults with Huntington disease (HD)-related chorea received placebo or valbenazine for 12 weeks. Top-line results demonstrated that once-daily valbenazine significantly improved chorea and was well tolerated (AAN 2022). KINECT-HD is the first Ph3 trial to implement the HD-HI, a novel, multidimensional, patient-reported outcome (PRO) validated to assess HD-related disease burden.
Design/Methods:
HD-HI includes 13 subscales (score range: 0=no disease burden to 100=highest disease burden) and a total score. Mean HD-HI scores at baseline, Wk10, and Wk12 were analyzed descriptively. Exploratory ANCOVA analyses were performed post hoc for HD-HI score changes from baseline.
Results:
Greater numerical decreases from baseline to Wk10 and Wk12 in HD-HI subscales were noted for valbenazine versus placebo in mobility (Wk10: -6.3 vs -4.1; Wk12: -4.2 vs -2.7), abnormal movements (Wk10: -12.2 vs -9.6; Wk12: -11.2 vs -4.3), and hand/arm function (Wk10: -7.2 vs -1.6; Wk12: -7.2 vs ‑1.4); however, baseline values were slightly higher in the valbenazine group for mobility and hand/arm function. Changes from baseline to Wk10 and Wk12 for fatigue and gastrointestinal health (including swallowing function) were unremarkable for valbenazine but also indicated no worsening. No meaningful changes in HD-HI total score were noted at Wk10 and Wk12. Least squares (LS) mean changes from baseline to Wk12 in the HD-HI abnormal movements subscale were -11.1 for valbenazine and -4.4 for placebo, with an LS mean difference between treatment groups of -6.7 (nominal P=0.0379).
Conclusions:
HD-HI results from KINECT-HD demonstrated the successful implementation of an HD-specific PRO during serial evaluation in the context of a Ph3 trial, along with reduced disease burden with valbenazine for abnormal movements, mobility, and hand/arm function in patients with HD-related chorea. This highlights the importance of monitoring changes in patient-reported disease burden in response to therapeutic interventions.