Chirag Shah, PharmD
Head, Strategic Publications & Medical Education
Medical Affairs, Neurocrine Biosciences, Inc.


“In clinical trials for valbenazine, approved for treating tardive dyskinesia (TD)—a persistent and potentially disabling movement disorder associated with exposure to prolonged antipsychotic medications or other dopamine receptor blocking agents—efficacy was based on mean changes from baseline in Abnormal Involvement Movement Scale (AIMS) total score,” explains Chirag Shah, PharmD, Head, Strategic Publications & Medical Education, Medical Affairs, Neurocrine Biosciences, Inc. “The AIMS total score was used to establish the effects of valbenazine on TD in three randomized, double-blind, placebo-controlled trials. However, these overall changes do not necessarily reflect patients’ individual experiences.”

To better understand the different patterns of improvement among patients with TD receiving valbenazine, Dr. Shah and colleagues conducted a post-hoc analysis of AIMS data from a long-term valbenazine study, KINECT 4, which included a 48-week open-label treatment period and a 4-week drug-free safety follow-up period (total of 52 weeks). The findings were presented at the recent American Psychiatric Association (APA) virtual Annual Meeting.

Patients Analyzed At Six Study Visits

In the post-hoc analysis, adults with schizophrenia/schizoaffective disorder or mood disorder and TD (n = 158) received open-label valbenazine (40 or 80 mg, per day) for up to 48 weeks. Descriptive analyses were conducted in participants receiving the study drug and having one or more post-baseline AIMS assessments.  Based on the minimal clinically important difference (MCID) for AIMS total score, the proportion of participants with a ≥2-point decrease (improvement) or ≥2-point increase (worsening) was analyzed by study visit (Weeks 4, 8, 12, 24, 36, and 48).

Based on the MCID for clinically meaningful response and protocol-defined (≥30% and ≥50% AIMS total score improvement from baseline, respectively), patients’ responses were categorized as follows:

– Early and sustained strong response (≥50% improvement by Week 4 through Week 48/last visit)
– Early and sustained response (≥30% improvement by Week 4 through Week 48/last visit)
– Early response (≥30% improvement at Week 4 and Week 48/last visit)
– Delayed response (≥30% improvement at Week 8 and Week 48/last visit)
– Late response (≥30% improvement at Week 12 or later and Week 48/last visit)
– Poor/no response (none of the five response groups)

Based on Schooler-Kane criteria for TD, “remission” was defined as absence of TD (ie, score of 2 [mild] in ≤1 AIMS item and all other item scores ≤1) and last available study visit and at last two visits “(sustained remission”).

Robust & Long-Term Improvement Expected

The study team found that the percentage of patients with ≥2-point improvement in AIMS total score increased over time: Week 4 (57.0%), Week 8 (78.5%), Week 12 (84.1%), Week 24 (95.1%), Week 36 (97.2%), and Week 48 (97.1%), Dr. Shah says, adding that three (2.9%) patients had ≥2-point worsening at Week 48.  “Patients met the different response criteria as follows: early and sustained strong repose, 10.8%; early and sustained response, 14.6%; early response, 3.2%; delayed response, 29.1%; and late response, 27.8%,” Dr. Shah notes. “Twenty-three (14.6%) patients had poor or no response, 98 (62.0%) patients met the criteria for remission, and 76 (48.1%) for sustained remission.”

Dr. Shah and colleagues conclude that patterns of improvement may vary among patients, but robust and long-term TD improvements can be expected with a once-daily dose of valbenazine. “Patients with a response within 4 weeks (‘early’ responders) may be likely to maintain that response throughout treatment,” he says. “Other may require 8 or more weeks of treatment before experiencing a response, but with long-term outcomes that are comparable to ‘early’ responders. Finally, some patients may achieve TD remission within 1 year of valbenazine treatment.”

Patterns of Improvement in Tardive Dyskinesia: Post-Hoc Analysis of a Long-Term Study With Valbenazine (KINECT 4)
Poster Presenter: Chirag Shah, PharmD
Lead Author: Christoph U. Correll, MD
Co-Authors: Tara Carmack, MS, Leslie Lundt, MD (Abstract 103)