Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder.

BACKGROUND Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. METHODS KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) 1:1 from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline): and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. RESULTS Efficacy analyses were conducted in 148 subjects (DBPC) and 125 subjects (VE) with SCHZ. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -2.9, d = 0.88; 40 mg, -1.6, d = 0.52; PBO, +0.3). AIMS score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -4.2; 40 mg, -2.5). By Week 52 (end of washout), AIMS scores were returning toward baseline levels, indicating re-emergence of TD. CGI-TD mean scores were as follows: Week 6 (80 mg, 3.0, d = 0.11; 40 mg, 2.9, d = 0.23; PBO, 3.2), Week 48 (80 mg, 2.2; 40 mg, 2.4), Week 52 (80 mg, 3.4; 40 mg, 3.3). AIMS responder rates (≥50% score reduction) were greater with VBZ than with PBO at Week 6 (80 mg, 40.9%, NNT = 4; 40 mg, 26.2%, NNT = 6; PBO, 9.3%), were increased at Week 48 (80 mg, 50.0%; 40 mg, 26.2%), and decreased after VBZ washout (80 mg, 21.6%; 40 mg, 9.5%). CGI-TD responder rates followed a similar pattern: Week 6 (80 mg, 29.5%, NNT = 17; 40 mg, 33.3%, NNT = 10; PBO, 23.3%), Week 48 (80 mg, 73.7%; 40 mg, 58.1%), Week 52 (80 mg, 29.7%; 40 mg, 33.3%). CONCLUSION Sustained TD improvements were found in subjects with SCHZ who received up to 48 weeks of VBZ, with TD reverting toward baseline when assessed 4 weeks after treatment withdrawal. Together with results from mood disorder subjects and the long-term safety profile (presented separately), these results indicate that long-term VBZ can be beneficial for managing TD regardless of psychiatric diagnosis category.