Skip to main content

Main menu

  • Home
  • Content
    • Current Issue
    • Ahead of Print
    • Past Issues
    • Supplements
    • Article Type
  • Specialty
    • Articles by Specialty
  • CME/MOC
    • Articles
    • Calendar
  • Info For
    • Manuscript Submission
    • Authors & Reviewers
    • Subscriptions
    • About CCJM
    • Contact Us
    • Media Kit
  • Conversations with Leaders
  • Conference Coverage
    • Kidney Week 2024
    • CHEST 2024
    • ACR Convergence 2023
    • Kidney Week 2023
    • ObesityWeek 2023
    • IDWeek 2023
    • CHEST 2023
    • MDS 2023
    • IAS 2023
    • ACP 2023
    • AAN 2023
    • ACC / WCC 2023
    • AAAAI Meeting 2023
    • ACR Convergence 2022
    • Kidney Week 2022
    • AIDS 2022
  • Other Publications
    • www.clevelandclinic.org

User menu

  • Register
  • Log in

Search

  • Advanced search
Cleveland Clinic Journal of Medicine
  • Other Publications
    • www.clevelandclinic.org
  • Register
  • Log in
Cleveland Clinic Journal of Medicine

Advanced Search

  • Home
  • Content
    • Current Issue
    • Ahead of Print
    • Past Issues
    • Supplements
    • Article Type
  • Specialty
    • Articles by Specialty
  • CME/MOC
    • Articles
    • Calendar
  • Info For
    • Manuscript Submission
    • Authors & Reviewers
    • Subscriptions
    • About CCJM
    • Contact Us
    • Media Kit
  • Conversations with Leaders
  • Conference Coverage
    • Kidney Week 2024
    • CHEST 2024
    • ACR Convergence 2023
    • Kidney Week 2023
    • ObesityWeek 2023
    • IDWeek 2023
    • CHEST 2023
    • MDS 2023
    • IAS 2023
    • ACP 2023
    • AAN 2023
    • ACC / WCC 2023
    • AAAAI Meeting 2023
    • ACR Convergence 2022
    • Kidney Week 2022
    • AIDS 2022

Chorea improvement in Huntington disease starts as early as week 2 with valbenazine

Presenter: Erin Furr Stimming, MD, University of Texas Health Science Center, Houston, TX

Chorea improvements over time with once-daily valbenazine treatment in adults with Huntington disease. Abstract 879. Presented August 29, 2023.


Improvements in chorea associated with Huntington disease (HD) were consistently greater with valbenazine treatment compared with placebo based on both physician and patient assessment during the 12-week phase 3 KINECT-HD study, reported Erin Furr Stimming, MD, University of Texas Health Science Center, Houston, and colleagues. Valbenazine is a highly selective vesicular monoamine transporter 2 inhibitor approved for tardive dyskinesia therapy.

Improvements in total chorea scores were significantly greater with valbenazine versus placebo at all postbaseline study treatment visits, with a reduction in the total maximal chorea (TMC) score observed as early as week 2, when study participants assigned to valbenazine were taking the starting dose (40 mg), and at all subsequent study treatment visits through week 12.

KINECT-HD was a double-blind placebo-controlled clinical trial of once-dailv oral valbenazine for the treatment of chorea associated with HD in 128 adults.1 The trial was performed in 46 Huntington Study Group sites in the United States and Canada. Participants with genetically confirmed HD and chorea (Unified Huntington Disease Rating Scale [UHDRS] TMC score ≥ 8) were randomized 1:1 to oral placebo or valbenazine for 12 weeks of treatment. Valbenazine was initiated at 40 mg and increased in 20-mg increments to a target dose of 80 mg once daily, depending on tolerability, during an 8-week dose-adjustment period. Of the 128 randomized participants, 125 were included in the full-set analysis. Among participants randomized to valbenazine, at week 12 (n = 55), 81.8% were taking 80 mg and 12.7% were taking 60 mg.

The mean UHDRS TMC score at baseline was 12.1 in the placebo arm and 12.2 in the valbenazine arm. The study met its primary endpoint — improvement in UHDRS TMC score from the screening and baseline periods to the maintenance period: minus 4.6 for valbenazine vs minus 1.4 for placebo (P < 0·0001) — demonstrating the superiority of valbenazine therapy. 

Two secondary endpoints for chorea improvement were also met, based on response status at week 12 for Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C). Approximately 42.9% of valbenazine recipients were GCI-I responders versus 13.2% of those assigned to placebo (P = 0.0007), and 52.7% and 26.4%, respectively, were PGI-C responders (P = 0.0062).

To assess the onset and trajectory of chorea improvements with valbenazine, prespecified exploratory analyses were performed for TMC score change, CGI-C response status, and PGI-C response status at each visit. At week 2, the mean UHDRS TMC score decreased by 2.9 points in the valbenazine arm compared with 1.6 points in the placebo arm (P < 0.007). At week 4, the declines were 4.1 and 2.1 points, respectively (P < 0.001). At week 12, the mean UHDRS TMC score had declined by 4.5 points in the valbenazine arm versus 1.2 points in the placebo arm (P < 0.001).

At week 14 (2 weeks after discontinuation of study drug), the observed TMC score for valbenazine was similar to that for placebo (11.1 vs 11.3), both having returned to the screening and baseline period values (valbenazine, 12.2; placebo, 12.1).

At all postbaseline study treatment visits, CGI-C and PGI-C responder rates were higher in the valbenazine group than in the placebo group. A significant difference between treatment groups was first detected at week 2 for PGI-C, with the initial 40-mg dose of valbenazine (P = 0.01), and at week 4 for CGI-C, after a dose increase to 60 mg (P = 0.01). At week 12, 42.9% of the valbenazine arm and 13.2% of the placebo arm met the GCI-C secondary endpoint (P < 0.001), defined as a GCI-C score of 2 or below, and 52.7% and 26.4%, respectively, met the PGI-C secondary endpoint (P < 0.01), defined as a PGI-C score of 2 or below.

In conclusion, the researchers stated in the abstract that these longitudinal exploratory endpoints provide evidence of the efficacy of valbenazine for reducing chorea associated with HD as early as 2 weeks at the initial 40 mg dose.

Reference

  1. Furr Stimming E, Claassen DO, Kayson E, et al. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington's disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2023; 22(6):494-504. doi: 10.1016/S1474-4422(23)00127-8.

Disclosure

This study was supported by Neurocrine Biosciences, Inc.

← Back to MDS 2023

Navigate

  • Current Issue
  • Past Issues
  • Supplements
  • Article Type
  • Specialty
  • CME/MOC Articles
  • CME/MOC Calendar
  • Media Kit

Authors & Reviewers

  • Manuscript Submission
  • Authors & Reviewers
  • Subscriptions
  • About CCJM
  • Contact Us
  • Cleveland Clinic Center for Continuing Education
  • Consult QD

Share your suggestions!

Copyright © 2025 The Cleveland Clinic Foundation. All rights reserved. The information provided is for educational purposes only. Use of this website is subject to the website terms of use and privacy policy. 

Powered by HighWire