Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia Is Associated With Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study

Robert A Hauser; Hadas Barkay; Hubert H Fernandez; Stewart A Factor; Joohi Jimenez-Shahed; Nicholas Gross; Leslie Marinelli; Amanda Wilhelm; Jessica Alexander; Mark Forrest Gordon; Juha-Matti Savola; Karen E Anderson

doi:10.3389/fneur.2022.773999

Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia Is Associated With Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study

Front Neurol. 2022 Feb 23:13:773999. doi: 10.3389/fneur.2022.773999. eCollection 2022.

Authors

Affiliations

¹ University of South Florida Parkinson's Disease and Movement Disorders Center, Tampa, FL, United States.
² Teva Pharmaceuticals, Netanya, Israel.
³ Cleveland Clinic, Cleveland, OH, United States.
⁴ Emory University, Atlanta, GA, United States.
⁵ Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁶ Teva Pharmaceuticals, West Chester, PA, United States.
⁷ Teva Pharmaceuticals, Basel, Switzerland.
⁸ Georgetown University, Washington, DC, United States.

Abstract

Background: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal studies, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores, with favorable safety/tolerability in TD patients. This study reports long-term efficacy and safety of deutetrabenazine in a 3-year, single-arm, open-label extension (OLE) study.

Methods: Patients who completed the pivotal studies could enroll in this single-arm OLE study, titrating up to 48 mg/day based on dyskinesia control and tolerability. Efficacy was assessed based on change from baseline in total motor AIMS score, Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC), and quality of life (QOL) assessments. Safety evaluation included adverse event (AE) incidence, reported using exposure-adjusted incidence rates, and safety scales.

Results: 343 patients enrolled in the study (6 patients were excluded). At Week 145 (mean dose: 39.4 ± 0.83 mg/day), mean ± SE change from baseline in total motor AIMS score was -6.6 ± 0.37 and 67% of patients achieved ≥50% improvement in total motor AIMS score. Based on CGIC and PGIC, 73% and 63% of patients achieved treatment success, respectively. QOL improvements were also observed. Deutetrabenazine was generally well tolerated, with low rates of mild-to-moderate AEs and no new safety signals; most safety scales remained unchanged over time.

Conclusions: Long-term deutetrabenazine treatment was associated with sustained improvement in AIMS scores, indicative of clinically meaningful long-term benefit, and was generally well tolerated. Results suggest deutetrabenazine may provide increasing benefit over time without increases in dose.

Keywords: deutetrabenazine; efficacy; safety; tardive dyskinesia; treatment.