Valbenazine Shows Efficacy for Chorea in Huntington Disease and Is Safe and Effective for Treatment of Tardive Dyskinesia in People Over Age 65
Valbenazine (Ingrezza; Neurocrine Biosciences, San Diego, CA) is the only selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for treatment of tardive dyskinesia (TD) that is available as a once-daily dose and does not require titration. Valbenazine can be dosed at 40, 60, or 80 mg/day (started at 40 mg/day and then increased to recommended dose of 80 mg/day) and does not have restrictions for how it is used, such as needing to be taken with food. Valbenazine is also being investigated as a potential treatment for chorea in Huntington disease (HD).
In the 12-week KINECT-HD (NCT04102579) phase 3 double-blind clinical trial, adults with Huntington disease who were treated with valbenazine (n=64) vs placebo (n=61) had improvement in chorea that was statistically significant as early as 2 weeks after starting treatment. Improvement in chorea was measured with the Total Maximal Chorea (TMC) score of the Unified Huntington’s Disease Rating Scale (UHDRS). Averaging the measurements at from weeks 10 and 12, participants treated with valbenazine vs placebo had a mean improvement of -4.6 vs -1.44 (P<.0001) points on the TMC, and improvement was maintained through week 12.
At week 12, the proportion of those treated with valbenazine vs placebo who had improvement on the Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C), respectively, was 42.9% vs 13.2% (P<.001) and 52.7% vs 26.4% (P<.01).
Adverse events were similar with valbenazine (76.6%; 49/64) and placebo (63.5%; 40/63), and most commonly were somnolence, fatigue, falls, urticaria/rash, and akathisia. No differences in vital signs, lab tests, or ECG parameters were observed in either group, and no increase in or worsening of suicidal ideation occurred with valbenazine treatment.
Eiry W. Roberts, MD, chief medical officer, Neurocrine Biosciences, said, "These positive data represent a major step forward in our commitment to offering a potential new treatment for HD. Results from KINECT-HD and our ongoing KINECT-HD2 study will form the basis of a supplemental application for valbenazine as a treatment of chorea in HD later this year."
Additionally, post hoc analysis of long-term data from clinical trials KINECT3 (NCT02274558) and KINECT4 (NCT02405091) of valbenazine for 48 weeks in participants with moderate-to-severe TD showed similar efficacy and safety in people age 65 or more compared with people under age 65. The 50% or more responder rates with 80 mg/day valbenazine on the Abnormal Involuntary Movement Scale (AIMS), for the 2 groups were 82.1% (23/28) and 63.6% (96/151), respectively, compared with 75% (6/8) and 50% (23/46) of those treated with 40 mg/day.
The safety profile was also similar for both groups, with no statistically significant differences in rates of adverse events. There was a slightly higher discontinuation rate because of adverse events in those age 65 and up, primarily due to somnolence. Across other discontinuations in that age group, there was no specific adverse event that correlated with discontinuation.
Dr. Roberts commented, "TD affects people of different ages who often use multiple medications. The number of concomitant medications also tends to increase with age. In that context, we felt it was very important it understand the relative tolerability and efficacy of Ingrezza in older patients."