Efficacy of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia: Results of a Long-Term Study (KINECT 3 Extension) (S56.005)

Objective: To assess the long-term efficacy of valbenazine (NBI-98854) in treating tardive dyskinesia (TD).

Background: Valbenazine is a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor in development for TD treatment. The efficacy and safety of valbenazine have been demonstrated in double-blind, placebo-controlled (DBPC) trials, with significant improvements found in Abnormal Involuntary Movement Scale (AIMS) dyskinesia total score (items 1–7) and Clinical Global Impression of Change (CGI-TD) score.

Design/Methods: KINECT 3 (phase 3 trial) included a 6-week DBPC period, 42-week valbenazine extension (VE) period, and 4-week treatment-free follow-up. Adults with TD and schizophrenia/schizoaffective disorder or mood disorder were enrolled; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC period were eligible for the VE period. Those initially randomized to placebo were re-randomized to valbenazine 80 or 40 mg/day; those randomized to valbenazine continued on same doses. Efficacy assessments included the AIMS (mean score changes, responders) and CGI-TD (mean scores, responders).

Results: 198 subjects entered the VE period; 124 completed treatment (80mg/day, n=63; 40mg/day, n=61) and 121 completed follow-up. At Week 48, AIMS results indicated TD improvement in both valbenazine dose groups: mean score changes (80mg/day, −4.8; 40mg/day, −3.0); responders (percent of subjects with ≥50% AIMS score reduction; 80mg/day, 52%; 40mg/day, 28%). However, AIMS scores increased from Week 48 to Week 52 (80mg/day, 6.2 to 9.8; 40mg/day, 6.8 to 8.4), indicating worsening of TD during the 4-week no-treatment period. Mean Week 48 CGI-TD scores demonstrated clinically meaningful global improvements (80mg/day, 2.1; 40mg/day, 2.4) with 76% and 59% of subjects (80mg/day and 40mg/day, respectively) rated as “much improved” or “very much improved.”

Conclusions: TD improved in subjects receiving valbenazine for 48 weeks, with TD reappearing after medication was withdrawn. Together with the long-term safety profile (presented separately), these results indicate that long-term valbenazine may be beneficial for managing TD.

Study Supported by: Neurocrine Biosciences, Inc.

Disclosure: Dr. Factor has received personal compensation for activities with Lundbeck, TEVA, Neurocrine, Avanir, Cynapsus, and Adamas as a consultant and from Uptodate as a speaker. Dr. Factor has received research support from Ipsen, Auspex/Teva, US World Meds, Pharm-Olam, Cynapsus Therapeutics, Solstice, CHDI Foundation, Michael J. Fox Foundation, NIH and Medtronic. Dr. Comella has received personal compensation for activities with Ipsen, Merz, Allergan, Medtronic, Teva, US World Meds, Impax, Acadia, Acorda, Revance, Neurocrine, Ultragenx Pharmaceuticals as a consultant. Dr. Correll has received personal compensation for activities with Alkermes, Allergan, Forum, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, Medavante, Medscape, Neurocrine, Otsuka as a consultant, advisor or speaker. Dr. Liang has received personal compensation from Neurocrine Biosciences, Inc. Dr. Burke has received personal compensation for activities with Neurocrine Biosciences, Inc. as an employee. Dr. O'Brien has received personal compensation for activities with Neurocrine Biosciences, Inc.