Erika Giraldo
Neurocrine Biosciences, Inc., San Diego, CA
Title: Long-Term Effects of Valbenazine for Tardive Dyskinesia in Patients with Schizophrenia/Schizoaffective Disorder or Mood Disorder: Pooled Post Hoc Analyses from KINECT 3 and KINECT 4
Biography
Biography: Erika Giraldo
Abstract
Introduction: Patients treated with antipsychotics, regardless of primary psychiatric diagnosis, are at risk for developing tardive dyskinesia (TD), a persistent and often irreversible movement disorder which is also potentially disruptive and disabling. Valbenazine (INGREZZA®) is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat TD in adults. The current objective was to evaluate the long-term effects of valbenazine on TD in adults with schizophrenia/schizoaffective disorder (SZD) or mood disorder (MD).
Methods: Pooled data were analyzed post hoc from two Phase 3 studies, KINECT 3 (NCT02274558) and KINECT 4 (NCT02405091) in adults with TD and SZD or MD. KINECT 3 had a 6-week double-blind placebo-controlled period, 42-week double-blind extension, and 4-week drug-free washout. KINECT 3 participants who were initially randomized to valbenazine continued into the extension period at the same dose (40mg or 80mg) and were included in this analysis.1,2 KINECT 4 participants initiated valbenazine dosing at 40mg and were escalated to 80mg if 40mg was tolerated and a clinician global rating was “minimally improved” or worse for a total of 48-weeks of open-label treatment with a 4-week drug-free washout. Participants could return to 40mg based on tolerability.3 TD was assessed using the Abnormal Involuntary Movement Scale (AIMS) total score (sum, items 1-7; scored by blinded central raters in KINECT 3 and site raters in KINECT 4) and Clinical Global Impression of Change -Tardive Dyskinesia (CGI-TD) scores (range from 1 “very much improved” to 7 “very much worse”). Psychiatric scales included Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) for SZD participants; or Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) for MD participants; and Columbia-Suicide Severity Rating Scale (C‑SSRS) for all participants.
Results: Analyses included 209 participants with SZD (40mg=75; 80mg=134) and 95 with MD (40mg=32; 80mg=63). At Week 48, significant mean (SEM) improvements from baseline were observed for AIMS total score: SZD (40mg, ‑5.0 [0.92]; 80mg, -8.5 [0.58]; both, P<0.0001); MD (40mg, ‑7.3 [1.58], P=.0004; 80mg: -8.5 [0.89], P<.0001). AIMS total score change from baseline to Week 52 (end of washout) showed some loss of effect. Similarly, at Week 48 CGI-TD mean (SEM) scores were: SZD (40mg, 2.2 [0.15]; 80mg, 1.9 [0.10]); MD (40mg, 2.3 [0.25]; 80mg: 1.7 [0.13]), indicative of “minimally improved” or better. Psychiatric status