These analyses will be presented at the 2025 Advanced Therapeutics in Movement & Related Disorders Congress hosted by the Parkinson & Movement Disorder Alliance in Washington, D.C.
"The KINECT-HD study demonstrated INGREZZA's ability to significantly reduce chorea, one of the most visible and disruptive symptoms of Huntington's disease, which often occurs alongside cognitive decline and leads to serious motor challenges," said Sanjay Keswani, M.D., Chief Medical Officer, Neurocrine Biosciences. "These new patient-reported analyses highlight INGREZZA's ability to reduce additional cognitive and motor-related challenges faced by those living with Huntington's disease, including memory loss, limitations with mobility and trouble swallowing."
In the 12-week Phase 3 KINECT-HD clinical trial, INGREZZA demonstrated a significant reduction in chorea severity, as measured by the Unified Huntington's Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score.
These post-hoc analyses were conducted to assess the effect of INGREZZA on motor and cognitive burden among people with Huntington's disease (HD) chorea using the Huntington's Disease Health Index (HD-HI), a disease-specific tool that was developed with patients and caregivers to assess disease burden across functional and psychological domains. Mean changes from baseline were evaluated at maintenance (defined as the average of Week 10 and Week 12 scores) across individual items from five HD-HI domains: cognition (18 items), mobility/ambulation (14 items), abnormal movements (7 items), hand/arm function (9 items) and gastrointestinal health (3 items). Outcomes were assessed among "affected" participants, defined as those with a baseline score of at least 2 on a given item (affected "a little" to "severely"). Reductions in scores indicate improvement.
Additional presentations at the 2025 ATMRD Congress include:
- Estimation of the Minimal Clinically Important Difference (MCID) and Longitudinal Change in the Tardive Dyskinesia Impact Scale (TDIS), a Validated, Tardive Dyskinesia-Specific, Patient-Reported Outcome Measure (Poster #P 47)
- Valbenazine Improves the Impacts and Symptoms of Tardive Dyskinesia: Topline Results from the Phase 4 KINECT-PRO™ Study (Poster #P 10)
- Effect Sizes of Once-Daily Valbenazine for Tardive Dyskinesia and Chorea Associated with Huntington's Disease: A Post-Hoc Analysis of Phase 3 Data (Poster #P 13)
- Sustained Chorea Improvements with Long-Term, Once-Daily Valbenazine in Adults with Huntington's Disease (Poster #P 14)
About Chorea Associated with Huntington's Disease:
Huntington's disease (HD) is a hereditary progressive neurodegenerative disorder in which the loss of certain neurons within the brain causes motor, cognitive and psychiatric symptoms. Symptoms generally appear between the ages of 30 and 50 years and worsen over a 10- to 25-year period. Most people with HD experience chorea, an abnormal involuntary movement disorder, characterized by irregular and unpredictable movements. Chorea can affect various body parts and interfere with motor coordination, gait, swallowing and speech. HD is estimated to affect approximately 41,000 adults in the U.S., with more than 200,000 at risk of inheriting the disease.
About KINECT®-HD:
KINECT®-HD was a Phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy of valbenazine as a once-daily treatment to reduce chorea associated with Huntington's disease (HD) and evaluate the safety and tolerability of valbenazine in patients with HD. The study enrolled 128 adults 18 to 75 years of age who were diagnosed with motor-manifest HD and who had sufficient chorea symptoms to meet study protocol criteria.
KINECT-HD used the Unified Huntington's Disease Rating Scale (UHDRS®) Total Maximal Chorea (TMC) score as the primary efficacy endpoint. The UHDRS is a comprehensive clinical rating scale developed by the Huntington Study Group to provide a uniform assessment of the clinical features and course of HD. It is comprised of motor, cognitive, behavioral, and functional assessments, along with an independence scale and total functional capacity measure. The TMC score is a component of the UHDRS motor assessment that measures the severity of chorea across seven different body regions (face, bucco-oral-lingual region, trunk, and all four limbs), with each region scored from 0 (no chorea) to 4 (marked/prolonged chorea), yielding a total possible score ranging from 0 to 28.
The secondary endpoints included Clinical Global Impression of Change (CGI-C) response status, a clinician-rated assessment of overall change from baseline, and Patient Global Impression of Change (PGI-C) response status, a patient-rated assessment of overall change from baseline, for valbenazine treatment. Both scales use a 7-point rating system ranging from "very much improved" (1) to "very much worse" (7), with "no change" (4) as the midpoint.
Treatment with valbenazine resulted in a placebo-adjusted mean reduction in the TMC score of 3.2 units (P<0.0001), indicating a substantial improvement in chorea. Secondary endpoints of CGI-C response status and PGI-C response status were also statistically significant and supported the improvements in TMC score that were seen over the 12-week study period.
Treatment-emergent adverse events in this study were generally consistent with the known safety profile of valbenazine. The most common adverse reactions in patients with HD included somnolence and sedation, urticaria, rash and insomnia.
About INGREZZA® (valbenazine) Capsules and INGREZZA® SPRINKLE (valbenazine) Capsules:
INGREZZA is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington's disease (HD). Only INGREZZA offers a therapeutic dose from day one with no required titration.
INGREZZA, developed by Neurocrine Biosciences, selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic or muscarinic receptors. While the specific way INGREZZA works to treat TD and HD chorea is not fully understood, INGREZZA is unique in that it selectively and specifically targets VMAT2 to inhibit the release of dopamine, a chemical in the brain that helps control movement. INGREZZA is believed to reduce extra dopamine signaling, which may lead to fewer uncontrollable movements.
INGREZZA is studied across the widest range of patients. It is always one capsule, once daily and can be taken together with most stable mental health regimens such as antipsychotics or antidepressants. Only INGREZZA offers the benefit of a sprinkle formulation, INGREZZA SPRINKLE, for those who experience dysphagia, have difficulty swallowing or prefer not to swallow a pill. INGREZZA and INGREZZA SPRINKLE dosages approved for use are 40 mg, 60 mg and 80 mg capsules.
About Neurocrine Biosciences, Inc.
Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders because you deserve brave science.
For more information, please visit www.neurocrine.com
