Movement Disorder Drug Shows Promise in Mid-Stage Study
VMAT2 inhibitor improves AIMS scores (January 6)
Positive results have been reported from a phase IIb trial of NBI-98854 (Neurocrine Biosciences), a small-molecule VMAT2 inhibitor, in patients with symptoms of tardive dyskinesia. The study’s primary endpoint was the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) at week 6.
At this time point, AIMS scores were reduced by 2.6 points in the NBI-98854 intention-to-treat (ITT) group compared with a reduction of 0.2 points in the placebo arm (P < 0.001). In addition, the responder rate (greater than or equal to 50% improvement from baseline) was 49% in the NBI-98854 ITT group compared with 18% in the placebo group (P = 0.002). In the per-protocol group, AIMS scores were reduced by 3.3 points in patients treated with NBI-98854 (P < 0.001), with a corresponding responder rate of 59% (P < 0.001).
The improvement in AIMS scores at week 6 was corroborated by the Clinical Global Impression–Tardive Dyskinesia (CGI-TD) scale. Treating clinicians determined that approximately 67% of the patients receiving NBI-98854 were “much improved” or “very much improved” at week 6 compared with 16% of placebo-treated subjects (P < 0.001).
The Kinect 2 trial was a randomized, parallel, double-blind, placebo-controlled, dose-titration, phase IIb clinical study of the capsule formulation of NBI-98854 in 100 patients with moderate-to-severe tardive dyskinesia with an underlying mood disorder (e.g., bipolar disorder), schizophrenia or schizoaffective disorder, or a gastrointestinal disorder with exposure to metoclopramide. The study assessed once-daily NBI-98854 over a 6-week placebo-controlled dosing period. Half of the randomized subjects received placebo and half received NBI-98854.
VMAT2 is a protein that is primarily responsible for repackaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) in presynaptic neurons in the brain. NBI-98854 is a highly selective VMAT2 inhibitor that modulates dopamine release during nerve communication.
Source: Neurocrine Biosciences; January 6, 2013.