(60) Valbenazine improves the impacts and symptoms of tardive dyskinesia: results from the phase 4 kinect-pro study

Background: : Once-daily valbenazine is a uniquely selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). KINECT-PRO is the first study to specifically assess and report the impacts of treating TD with a VMAT2 inhibitor using multiple validated patient-reported outcomes (PROs).

Objective: : The primary objective of this open-label valbenazine study was to evaluate patient-reported changes in the impact of TD using multiple validated PROs. The secondary objective was to evaluate clinician- and patient-reported changes in TD severity and symptoms.

Methods: : This study included: screening (4 weeks); treatment with valbenazine 40 mg (4 weeks); continuation with 40 mg or increase to 60 or 80 mg (12 weeks); stable dosing with 40, 60, or 80 mg (8 weeks); and safety follow-up (2 weeks). Participants had mild-to-severe TD severity and mild-to-severe associated distress (per Abnormal Involuntary Movement Scale [AIMS] items 8 and 10). PROs included the Tardive Dyskinesia Impact Scale (TDIS), Sheehan Disability Scale (SDS), and EuroQoL Group’s EQ Visual Analog Scale (EQ-VAS). Mean changes from baseline (CFB) for PROs and AIMS total score were analyzed by TD severity (mild or moderate/severe), psychiatric diagnosis (schizophrenia/schizoaffective disorder [SCHZ] or major depressive disorder/bipolar disorder [MOOD]), and overall.

Results: : Of 59 enrolled participants (TD-mild [n=24], TD-moderate/severe [n=35], SCHZ [n=27] MOOD [n=32]), 52 completed the Week 24 visit (end of stable-dose treatment); 45 had PRO and AIMS data at Week 24. In participants overall, PRO and AIMS improvements were observed from Week 4 through end of treatment. Mean CFB at Wk24 in participants overall and by TD severity were: TDIS (-8.0, -6.8, -8.9 [overall, TD-mild, TD-moderate/severe]); SDS-social life (-2.3, -1.8, -2.8); SDS-family life (-1.6, -1.3, -1.8); EQ-VAS (+13.1, +12.8, +13.3); AIMS (-6.8, -5.6, -7.8). In psychiatric diagnosis subgroups, mean CFB were: TDIS (-5.8, -9.7 [SCHZ, MOOD]); SDS-social life (-1.6, -2.9); SDS-family life (-0.7, -2.3); EQ-VAS (+8.3, +17.0); AIMS (-5.8, -7.6). Safety and tolerability were consistent with the known profile of valbenazine, with no new concerns identified.

Conclusions: : Robust and sustained improvements in physical, social, and emotional functioning with valbenazine, along with a large reduction in TD symptoms, were observed in the overall study population and all subgroups.

Sponsorship:: Neurocrine Biosciences, Inc.