Open-Label Extension of KINECT: A Phase 2 Study of Valbenazine (NBI-98854) for Tardive Dyskinesia (S27.001)

Objective: To assess safety, tolerability and persistence of effect of valbenazine in subjects with schizophrenia or schizoaffective disorder with moderate to severe Tardive Dyskinesia (TD). Background: TD is a drug-induced movement disorder in subjects chronically exposed to dopamine antagonists. Valbenazine is a novel, highly selective inhibitor of vesicular monoamine transporter 2 (VMAT2) that demonstrated a favorable safety profile in early Phase 1 and 2 studies. Design/Methods: Eighty subjects completing the 6-week double-blind, placebo-controlled KINECT trial (NCT01688037) participated in this 6-week open-label extension, during which all subjects received valbenazine 50mg once daily from Weeks 6 through 12. TD was scored by a blinded central rater using video recordings of the Abnormal Involuntary Movement Scale (AIMS). Subjects underwent clinical and safety assessments, including measurements of psychiatric symptoms. Results: There were marked reductions in AIMS dyskinesia scores (mean change of -5.8 from baseline mean of 12.8) for subjects receiving valbenazine from Weeks 6 through 12. The overall responder rate, as defined by a ≥50[percnt] AIMs reduction from baseline, was 54[percnt]. The Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) assessed by each site’s investigator demonstrated clinically meaningful improvement (61[percnt] “much improved” or “very much improved”). There were no treatment-related serious adverse events and no evidence for emergent parkinsonism, akathisia or suicidal ideation. There were no hematology, chemistry or ECG safety signals. Conclusions: Valbenazine at 50mg once daily during this 12-week treatment period was associated with a marked reduction in TD severity as measured by the AIMS and CGI-TD. The magnitude of AIMS reduction from Week 6 to 12 in the former placebo recipients was equal to that of the valbenazine recipients in the initial 6 weeks of the trial, consistent with pharmacological effect. TD subjects with schizophrenia or schizoaffective disorder appeared to tolerate valbenazine well. Additional trials with valbenazine are in progress. Disclosure: Dr. Bari has nothing to disclose. Dr. Shiwach has received research support from Neurocrine Biosciences, Inc. Dr. Jimenez has received personal compensation for activities with Neurocrine Biosciences, Inc. as an employee. Dr. Siegert has received personal compensation for activities with Neurocrine Biosciences, Inc. as an employee. Dr. O9Brien has received personal compensation for activities with Neurocrine Biosciences, Inc., as an employee. Dr. O9Brien holds stock and/or stock options in Neurocrine Biosciences, Inc.