Objective: To assess the efficacy, safety and tolerability of valbenazine (NBI-98854) for Tardive Dyskinesia (TD).

Background: Tardive dyskinesia (TD) is a persistent and often disabling movement disorder resulting from chronic antipsychotic exposure. There are currently no FDA-approved treatments for TD. Valbenazine is a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor with favorable efficacy and safety profiles in Phase 1 and 2 studies.

Methods: In this Phase 3, double-blind, parallel-group, six-week, placebo-controlled trial, subjects with moderate or severe neuroleptic-induced TD and underlying schizophrenia, schizoaffective disorder, or mood disorder were randomized 1:1:1 (placebo: 40mg valbenazine: 80mg valbenazine, once daily). The primary outcome was an intention-to-treat (ITT) analysis of change from baseline on the Abnormal Involuntary Movement Scale (AIMS) total score, assessed by blinded central raters, for the 80mg dose vs placebo. Safety assessments included adverse event (AE) rates, laboratory, ECG, and psychiatric assessments.

Results: Sixty-four sites randomized 234 subjects. Most subjects had schizophrenia or schizoaffective disorder, and 86% were receiving concomitant antipsychotic medications (16% typical, 77% atypical). The mean baseline AIMS score (SD) was 10.1 (4.0). Valbenazine 80mg resulted in a significant improvement in AIMS score vs placebo (LS Mean change from baseline -3.2 vs -0.1; P<0.0001). The AIMS score was also reduced in the 40mg group vs placebo (LS Mean change from baseline -1.9 vs -0.1; P=0.0021; full description of supportive analyses to be presented). Adverse events were similar among all groups and were consistent with those of prior studies; the most commonly reported AE was somnolence (80mg: 5%, 40mg: 4%, placebo: 4%). Three percent of subjects discontinued due to treatment-emergent AEs (80mg: 4%, 40mg: 3%, placebo: 3%).

Conclusions: Once-daily administration of valbenazine was associated with a significant improvement in TD vs placebo in subjects with schizophrenia, schizoaffective disorder or mood disorder. Both valbenazine doses were generally well tolerated, even as patients were taking a wide range of concomitant medications, including antipsychotic agents. Valbenazine may be a promising therapy for TD.

Submitted but pending acceptance: American Academy of Neurology, April 15-21, 2016.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/kinect-3-a-randomized-double-blind-placebo-controlled-phase-3-trial-of-valbenazine-nbi-98854-for-tardive-dyskinesia/