Valbenazine well-tolerated, improved chorea associated with Huntington’s disease

Key takeaways:

• Mean change from baseline in UHDRS TMC score was more significant in patients treated with valbenazine compared with placebo.
• Valbenazine was well-tolerated with few treatment-emergent adverse events.

Treatment with valbenazine at doses up to 80 mg once daily was generally well-tolerated and significantly improved chorea compared with placebo in adults with Huntington’s disease, according to research in The Lancet Neurology.

“Approximately 90% of individuals with adult-onset Huntington’s disease exhibit chorea during their disease course,” Erin Furr-Stimming, MD, professor of neurology at McGovern Medical School at the University of Texas Health Science Center at Houston, and colleagues wrote. “Although tetrabenazine and deutetrabenazine have clearly demonstrated efficacy in treating chorea, some individuals with Huntington’s disease might need or want to try other treatments for tolerability reasons or for easier titration and dosing.”

Researchers evaluated the vesicular monoamine transporter 2 inhibitor valbenazine in patients with chorea associated with Huntington’s disease in the phase 3, randomized, double-blind, placebo-controlled KINECT-HD study, which was conducted at 46 Huntington Study Group sites in the United States and Canada.

They enrolled 128 adults with genetically confirmed Huntington’s disease and chorea, with a score of at least 8 on the Unified Huntington’s Disease Rating Scale [UHDRS] Total Maximal Chorea [TMC] scale. Participants were randomized 1:1 to receive oral valbenazine 40 mg once daily for 2 weeks, increasing to a target dose of 80 mg per day if well-tolerated, or placebo for 12 weeks.

The primary outcome was mean change in UHDRS TMC score from baseline to the maintenance period (average of weeks 10 and 12 assessments). Researchers also monitored safety via treatment-emergent adverse events, vital signs, ECGs and laboratory and clinical tests.

Of those initially enrolled, 125 patients were included for final analysis (valbenazine, n = 64; placebo, n = 61) and 127 for safety analysis (valbenazine, n = 64; placebo, n = 63).

According to results, mean changes from baseline to maintenance in UHDRS TMC scores were –4.6 for valbenazine and –1.4 for placebo (least-squares mean difference = –3.2; 95% CI, –4.4 to –2), a significant reduction that met the study’s primary endpoint.

In addition, valbenazine was generally well-tolerated, with the most commonly reported treatment-emergent adverse events including somnolence (16%), fatigue and falls. One participant in the valbenazine group experienced a serious treatment-emergent adverse event (angioedema due to food allergy) compared with two patients in the placebo group (colon cancer and psychosis).

Researchers reported no clinically significant changes in vital signs, ECGs or laboratory tests and no indication of suicidal behavior in the valbenazine group.

“The results of KINECT-HD support the efficacy of valbenazine in individuals with chorea associated with Huntington’s disease,” Furr-Stimming and colleagues wrote.