VMAT2 Inhibitor Helpful in Treating Chorea Symptoms Associated with Huntington Disease

Results from the phase 3 KINECT-HD study, published in The Lancet Neurology online edition and pending publication in the journal’s June 2023 print issue, suggest that the vesicular monoamine transporter 2 (VMAT2) inhibitor Ingrezza (valbenazine; Neurocrine Bioscience, San Diego, CA) may improve chorea symptoms associated with Huntington disease (HD). Individuals diagnosed with HD with chorea symptoms who were treated with Ingrezza experienced a significant reduction in the frequency and severity of chorea symptoms beginning at week 2 of treatment along with improvements in patient reported quality of life measurements over the course of the study. Most patients with HD experience chorea, a symptom associated with irregular and unpredictable movement.

KINECT-HD was a randomized double-blind placebo-controlled phase 3 study that included 128 patients at 46 Huntington’s Study Group (HSG)-credentialed sites across North America. As a primary endpoint, the study assessed the reduction of chorea severity measured by least-squares mean change from weeks 2 to 12 in United Huntington’s Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC). Secondary endpoints included Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C) response statuses as well as safety assessments. There were only mild-to-moderate treatment-emergent adverse events reported in those taking Ingrezza, including somnolence, fatigue, fall, and akathisia.

“There remains a need for symptomatic treatments for chorea associated with Huntington’s disease,” said study author Erin Furr Stimming, MD, “and this manuscript provides an in-depth overview of the KINECT-HD study data and potential of valbenazine to fulfill this need.”

In December 2022, the Food and Drug Administration (FDA) accepted the supplemental New Drug Application for Ingrezza as a treatment for chorea associated with a Prescription Drug User Fee Act target action date of August 20, 2023.