Publication of full KINECT-HD Phase III study results of valbenazine for the treatment of chorea associated with Huntington's disease in the Lancet Neurology.- Neurocrine Biosciences.

The study met pre-defined primary and secondary endpoints of improvement in chorea severity and global impression of change, demonstrating a reduction in chorea symptoms associated with HD and improvement of overall chorea severity as noticed by clinicians and patients, with improvement seen as early as Week 2 of the initial dose in the 12-week study.

Valbenazine is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor. VMAT2 inhibitors have been shown to reduce chorea associated with HD.

"More than 90 percent of adults with HD experience chorea," said Erin Furr Stimming, M.D., the paper's lead author and professor in the Department of Neurology and Memorial Hermann Chair with McGovern Medical School at UTHealth Houston. "The KINECT-HD study data demonstrated statistically significant improvement in chorea associated with HD as compared with placebo. The safety profile for participants with chorea associated with HD was consistent with the known safety profile of valbenazine. By the end of the 12-week study, 82 percent of valbenazine-treated participants were taking 80 mg."

The KINECT-HD randomized double-blind, placebo-controlled Phase III study was conducted with 128 participants at 46 Huntington Study Group (HSG)–credentialed sites in North America The primary endpoint was a reduction in severity of chorea, the cardinal motor feature in HD, as measured by change in the Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) score from baseline to the average score at weeks 10 and 12. The TMC score is part of the motor assessment of the UHDRS that measures chorea.

In the KINECT-HD study, treatment with valbenazine resulted in a placebo-adjusted mean reduction in the TMC score of 3.2 units (P < 0.0001), indicating a highly statistically significant improvement in chorea. Improvement was seen at Week 2 as participants completed the lowest study dose (40 mg), with consistently greater improvement relative to placebo in all subsequent visits (Weeks 4 to 12), as the dose was adjusted from 40 mg to 60 mg and 80 mg over the course of the 12-week study. Secondary endpoints of Clinical Global Impression of Change (CGI-C) response status and Patient Global Impression of Change (PGI-C) response status were also statistically significant and supported the improvements in TMC score that were seen over the 12-week study period. At Week 12, more participants were classified as "much improved" or "very much improved" according to these key secondary endpoints when treated with valbenazine than placebo (CGI-C: 43 percent versus 13 percent; PGI-C: 53 percent versus 26 percent). No statistical difference between treatment groups was found in either of the two secondary Quality of Life in Neurological Disorders (Neuro-QoL) endpoints.

Treatment-emergent adverse events, including somnolence, fatigue, fall and akathisia, were mild to moderate and consistent with the known safety profile of valbenazine. No suicidal behavior or worsening of suicidal ideation was observed in the valbenazine-treated subjects in this study.

The KINECT-HD study marked the first-ever implementation of the Huntington's Disease Health Index (HD-HI) in a Phase III trial. HD-HI is a novel, validated, disease-specific, patient-reported outcome measure designed to evaluate clinically meaningful changes in HD function in response to therapeutic interventions. The HD-HI study results of these exploratory endpoints demonstrate improvement in mobility and hand/arm function and decreased burden from abnormal movements, as reported by patients receiving valbenazine compared to placebo.

See- "Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington's disease (KINECT-HD): a phase III, randomised, double-blind, placebo-controlled trial"-Prof Erin Furr Stimming, MD, Daniel O Claassen, MD, Elise Kayson, MS. Jody Goldstein, BS.Raja Mehanna, MD. Hui Zhang, Ph, et al. Published: June, 2023DOI:https://doi.org/10.1016/S1474-4422(23)00127-8. VOLUME 22, ISSUE 6, P494-504, JUNE 2023.