Valbenazine (Ingrezza; Neurocrine Biosciences) demonstrates sustained efficacy and safety in treating Huntington's disease (HD) chorea, according to interim data from the open-label extension study KINECT-HD2 (NCT04400331). The study, presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders, revealed that once-daily valbenazine provided clinically meaningful benefits for up to one year, irrespective of background antipsychotic therapy.
The KINECT-HD2 study included 125 patients with HD who received at least one dose of valbenazine. Led by Erin Furr Stimming, MD, professor of neurology at McGovern Medical School of UTHealth Houston, the study assessed the long-term effects of valbenazine on chorea, a common and debilitating symptom of Huntington's disease.
Sustained Improvement in Chorea Symptoms
Improvements in the Total Maximal Chorea (TMC) score on the Unified Huntington’s Disease Rating Scale (UHDRS) were observed as early as week 2, with an initial valbenazine dose of 40 mg (–3.4 [±3.1]; n = 118). These improvements were sustained from week 8 (–5.6 [±3.6]; n = 110) to week 50 (–5.8 [±4.1]; n = 66) at doses up to 80 mg. The mean TMC score at baseline was 11.9 (±3.5). Notably, the improvements were consistent whether or not patients were also receiving antipsychotic treatment.
According to Eiry W. Roberts, MD, chief medical officer at Neurocrine, "The data from this study reinforce the long-term clinical safety of INGREZZA observed to date, showing sustained improvement in chorea regardless of antipsychotic use during the study. This is an important finding given that approximately a third of patients living with Huntington's disease chorea are prescribed antipsychotic medications for neuropsychiatric symptoms without receiving treatment for the chorea that may significantly disrupt daily life."
Safety Profile and Adverse Events
Of the 125 participants, 119 (95.2%) reported at least one treatment-emergent adverse event (TEAE), and 17 (13.6%) discontinued due to a TEAE. The most common TEAEs were falls (30.4%), fatigue (24.0%), and somnolence (24.0%).
KINECT-HD Study Context
The KINECT-HD2 study design mirrored the original KINECT-HD trial, which included adults aged 18 to 75 years diagnosed with manifest HD or motor manifest HD exhibiting sufficient chorea symptoms. In KINECT-HD, valbenazine met its primary endpoint, demonstrating a statistically significant placebo-adjusted reduction in UHDRS TMC score of 3.2 units (P < .0001) from baseline to weeks 10 and 12.
Additional data from KINECT-HD showed improved chorea as early as 2 weeks after administration of the lowest dose (40 mg), with consistently greater improvement relative to placebo in subsequent visits (weeks 4 to 12), as the dose was adjusted from 40 mg to 60 mg to 80 mg over the 12-week period. The study also met its secondary endpoints on change in Clinical Global Impression-Clinician (CGI-C) and Patient Global Impression-Clinician (PGI-C). By the end of the 12-week period, 43% and 53% of patients on valbenazine were classified as "much improved" or "very much improved" on CGI-C and PGI-C, respectively, compared with rates of 13% and 26% for those on placebo.
Valbenazine Formulation and Availability
In early 2024, the FDA approved a new sprinkle formulation of valbenazine to enhance administration options and flexibility. The oral granule capsules (40 mg, 60 mg, and 80 mg) are designed to be opened and sprinkled on soft foods before administration. The approval was based on data demonstrating bioequivalence and tolerability compared to the original valbenazine capsules.
