Valbenazine decreases disease burden in patients with chorea associated with Huntington disease
Presenter: Dietrich Haubenberger, MD, Neurocrine Biosciences, San Diego, CA
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. Abstract 11-012. Scientific poster session 2. Presented April 23, 2023.
Once-daily administration with valbenazine significantly improves symptoms of chorea associated with Huntington disease (HD), according to results of the KINECT-HD trial based on the Huntington Disease Health Index (HD-HI). The index was developed to reflect the physical, mental, and social issues and symptoms that have the greatest impact on patients with HD. It was based on guidance from the Food and Drug Administration (FDA) on patient-reported outcomes for clinical trials,
“KINECT-HD is the first phase III trial to implement the HD-HI,” Haubenberger said. He noted that the trial highlights the importance of monitoring changes in patient-reported disease burden in response to therapeutic intervention.
In the randomized, double-blind, placebo-controlled KINECT-HD trial, 125 adults with HD-related chorea received valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor (64 patients), or placebo (61 patients) for 12 weeks. Top-line results showed that a single daily dose of valbenazine significantly improved chorea and was well tolerated, according to presenter Dietrich Haubenberger, MD, of Neurocrine Biosciences in San Diego, CA.
Valbenazine is FDA-approved for tardive dyskinesia and is under investigation as a potential treatment for chorea associated with HD.
The HD-HI includes 13 subscales and a total score ranging from 0 (no disease burden) to 100 (highest disease burden). The total score is the average of the 13 subscale scores. Mean HD-HI scores at baseline, week 10 and week 12 were analyzed.
Among the 122 patients with available assessments at baseline, subscale scores in the valbenazine group were slightly higher (worse) for mobility and hand/arm function and slightly lower (better) for emotional health, social satisfaction, fatigue, and cognition.
Numerical changes at week 12 were comparable to those at week 10 and indicated greater magnitude of improvement with valbenazine versus placebo in total score and in 8 of 13 subscale scores, including mobility, abnormal movements, hand and arm function, emotional health, social performance, social satisfaction, cognition, and gastrointestinal health/swallowing function.
At week 12, there was meaningful worsening in fatigue and daytime sleepiness in valbenazine-treated patients. The impact of pain on overall disease burden worsened from week 10 to week 12 and was reported in greater magnitude in the placebo group.
Among the 8 subscales with greater valbenazine improvements relative to placebo at week 12, post hoc analyses indicated that those with the largest least-square mean differences between treatment groups were abnormal movements, emotional health, hand and arm function, cognition, and social satisfaction. A statistically significant difference was found for abnormal movement at week 12 (P = .0379).
In conclusion, Haubenberger said, “In this study, greater reduction in HD-related disease burden was reported with valbenazine versus placebo in domains that are particularly affected among individuals experiencing chorea (abnormal movements, hand and arm function, mobility). Greater improvements with valbenazine relative to placebo were also found in domains related to emotional and social well-being, cognition and gastrointestinal health/swallowing. Results also indicate that HD-HI was a sensitive measure of patient-related, disease-related burden in this study population and a useful tool for capturing such changes in future clinical trials of HD therapies.”
References
Heatwole C, Furr Stimming E, Claasen DO, et al. 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. Presented at the 75th Annual Meeting of the American Academy of Neurology, April 23, 2023.
Brumfield OS, Zizzi CE, Dilek N, et al. The Huntington's Disease Health Index: Initial evaluation of a disease-specific patient reported outcome measure. J Huntingtons Dis 2022; 11(2):217-226. doi:10.3233/JHD-210506.
Glidden AM, Luebbe EA, Elson MJ, et al. Patient-reported impact of symptoms in Huntington disease: PRISM-HD. Neurology. 2020 May 12; 94(19):e2045-e2053. Epub 2020 Mar 19.
Furr Stimming E, et al. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntingtons Disease (KINECT-HD): a phase 3 randomized, double-blind, placebo-controlled trial. Lancet Neurol 2023; in press.
Disclosures
Dietrich Haubenberger has received compensation for serving as an employee of Neurocrine Biosciences and he has stock in Neurocrine Biosciences. He also has a noncompensated relationship as a member of the Board with American Society for Experimental Neurotherapeutics that is relevant to AAN interests or activities.