Deutetrabenazine Demonstrates Sustained Benefit in Treating Tardive Dyskinesia

Martha Sajatovic, MD

Findings from a 3-year post-hoc analysis of patients who completed the ARM-TD or AIM-TD studies (NCT02195700; NCT02291861) showed that long-term treatment with deutetrabenazine (Austedo; Teva Pharmaceuticals) was well-tolerated and associated with sustained improvement in total motor Abnormal Involuntary Movement Scale (AIMS) score, treatment success, and improved quality of life in both older and younger patients with tardive dyskinesia (TD).^1,2

At the conclusion of the 3-year period, both the younger (n = 119 [<55 years]) and older (n = 218 [≥5 years]) subgroups experienced reductions of –6.7 (standard error [SE], 0.62) and –6.5 (SE, 0.47), respectively, in total motor AIMS score. These reductions were observed early and were sustained at week 145 (percent changes, –61.4% [SE, 4.10%] and –54.6% [3.01%], respectively). Furthermore, 76% of younger participants and 62% of older participants achieved at least 50% improvement in total motor AIMS score from baseline.

Lead author Martha Sajatovic, MD, professor, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, and colleagues assessed change and percent change from baseline in AIMS score, response rates for 50% or more AIMS improvement, Clinical Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), and safety of deutetrabenazine.

"This analysis helps further our understanding of AUSTEDO as a treatment that may help alleviate uncontrolled movements in adults but is particularly compelling when considering treatment of older patients," Sajatovic said in a statement.¹ "Symptoms of TD can worsen in severity over time, especially in patients 55 years and older who have had long-term treatment with an antipsychotic prescription. As this occurs, they may experience balance and coordination issues, putting them at an increased risk for falls that may be especially concerning."

The open label extension study included 337 participants with TD who were washed out from their phase 3 study drug for 1 week, then started deutetrabenazine at 12 mg/day (6 mg twice daily) regardless of previously treatment. Over a 6-week titration phase, deutetrabenazine was increased weekly by 6 mg/day using a response-driven dosing regimen until adequate dyskinesia control was achieved, a clinically significant adverse event (AE) occurred, or a maximum dose of 48 mg/day was achieved.

Investigators observed that a majority of participants achieved treatment success at weeks 54, 106, and 145 based on CGIC and PGIC. At the final week, 67% of younger participants (37 of 55) and 76% of older participants (80 of 105) achieved treatment success on the GCIC, while 64% (35 of 55) and 63% (67 of 106)of the same groups, respectively, achieved success on the PGIC.

Treatment with deutetrabenazine positively impacted quality of life for patients with TD, as represented by improvements on modified Craniocervical Dystonia Questionnaire (mCDQ-24) scores across both subgroups. More specifically, these improvements were seen across the stigma, emotional, pain, activities of daily living, and social domains.

Deutetrabenazine was found to be well-tolerated among both subgroups. Exposure-adjusted incidence rates (EAIRs), calculated for adverse events (AEs) as the number of participants per patient-year, were 1.05 and 1.36 for any AE in younger and older participants, respectively. EAIRs for serious AEs were 0.08 in the younger subgroup and 0.12 in the older subgroup. There were 8 deaths in total, all occurring in the older subgroup and none of which were deemed related to the study drug.

The Teva product is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor and has been approved by the FDA for the treatment of TD in adults and for the treatment of chorea associated with Huntington disease (HD) since August 2017 and April 2017, respectively.

REFERENCES

1. Teva announces post hoc analysis of long-term data examining treatment with Austedo (deutetrabenazine) tablets in adult patients with tardive dyskinesia. News release. Teva. August 20, 2021. Accessed August 23, 2021. https://www.businesswire.com/news/home/20210820005032/en/Teva-Announces-Post-Hoc-Analysis-of-Long-Term-Data-Examining-Treatment-with-AUSTEDO%C2%AE-deutetrabenazine-Tablets-in-Adult-Patients-with-Tardive-Dyskinesia

2. Sajatovic M, Finkbeiner S, Wilhelm A, et al. Deutetrabenazine in younger and older patients with tardive dyskinesia. Am J Geriatr Psychiatry. Published online August 16, 2021. doi: 10.1016/j.jagp.2021.08.003.