Abstract Details

Chorea is a hallmark motor symptom of HD impacting motor function. Valbenazine, a potent and selective vesicular monoamine transporter 2 inhibitor was approved for the treatment of tardive dyskinesia in the US (2017).  

KINECT-HD evaluated the efficacy, safety, and tolerability of valbenazine for the treatment of chorea associated with Huntington Disease (HD). 

KINECT-HD, a Phase 3, randomized, double-blind, 12-week, placebo-controlled study in North America, enrolled 128 adults 18 to 75 years of age with chorea and genetically confirmed HD. Participants randomized 1:1 (placebo: valbenazine, once daily) were initiated with 40mg and titrated up to 80mg as tolerated. Primary outcome was change in chorea severity, using the Total Maximal Chorea (TMC) score of the Unified Huntington's Disease Rating Scale (UHDRS®) from baseline (average score at screening and baseline visit) to the maintenance period (average score at weeks 10 and 12). Safety assessments included adverse event (AE) rates, laboratory, ECG, and psychiatric assessments. Secondary outcome measures included clinician and patient-reported outcomes. 

Average TMC score during the baseline period was 12.2 (SD 2.3). Valbenazine demonstrated a statistically significant improvement in chorea severity with a placebo-adjusted mean reduction of 3.2 units in TMC score vs. placebo (LS Mean change from baseline -4.6 vs. -1.4; P<0.0001). Statistically significant secondary endpoints of Clinical Global Impression of Change (CGI-C) Response Status and Patient Global Impression of Change (PGI-C) Response Status favored valbenazine treatment. Neuro-QOL upper and lower extremity physical function endpoints were not statistically significant. Most commonly reported AE was somnolence (valbenazine: 15.6%, placebo: 3.2%). No suicidal behavior or worsening of suicidal ideation was observed in the valbenazine treated subjects.

Once-daily administration of valbenazine was associated with significant improvement in chorea. Valbenazine was well tolerated; treatment emergent adverse events observed in this trial were consistent with the known safety profile of valbenazine.