Article
No Sign of New Movement Disorders from Long-term Valbenazine for TD
Author(s):
85% of subjects also took antipsychotic medications, usually atypical agents.
Tardive dyskinesia (TD) is an involuntary movement disorder that results from extended exposure to dopamine-receptor antagonists such as antipsychotic agents. By inhibiting vesicular monoamine transporter 2 and thereby reducing synaptic dopamine levels, valbenazine (Ingrezza) can modulate dopaminergic neurotransmission and reduce symptoms of TD. As a result, the US Food and Drug Administration (FDA) approved valbenazine to treat TD this year.
Blocking the D2 receptor may also result in acute or delayed symptoms of movement disorders such as akathisia (restlessness) or parkinsonism. To assess the emergence of these symptoms during long-term (≤48 wk) valbenazine therapy in adults with TD and schizophrenia or schizoaffective disorder or a mood disorder, a research team analyzed pooled long-term exposure (LTE) data from 3 clinical trials of valbenazine.
In these studies, which were part of the KINECT series, subjects received valbenazine at doses of 40 mg, 50 mg, or 80 mg, depending on the study. Stephanie Lessig, MD, (pictured) an associate professor in the Department of Neurosciences at the University of California at San Diego School of Medicine in San Diego, California, led the research team, which analyzed all outcomes descriptively.
The team analyzed data from 430 subjects in the pooled LTE safety population, defined as all patients who received at least 1 dose of valbenazine. In this population, 72% had schizophrenia or schizoaffective disorder, and 28% had a mood disorder such as bipolar disorder or major depressive disorder. Baseline demographics and disease characteristics were similar between valbenazine dose groups, and 85% of subjects also took antipsychotic medications, usually atypical agents.
Assessments included the percentage of subjects with treatment-emergent adverse events (TEAEs) that could have been related to a movement disorder. The team also analyzed mean changes from baseline in the Barnes Akathisia Rating Scale (BARS) total and global scores by study visit, including the follow-up visit after treatment washout at week 52. Analysis by study visit also included mean changes from baseline in the Simpson-Angus Scale (SAS) global score, a 10-item clinician-rated assessment of parkinsonian extrapyramidal signs such as gait, rigidity, or tremor.
As a result, the team found that incidences of movement disorder-related TEAEs were low and similar between treatment groups. Mean changes from baseline in BARS total and global scores and in SAS global score were generally small and similar between groups as well.
These results led the team to conclude that, although most subjects took antipsychotics along with valbenazine during the long term, they had a low incidence of TEAEs that could have been related to movement disorders. Moreover, the team noted that BARS and SAS mean score changes from baseline provided no indication of treatment-emergent akathisia or parkinsonism from long-term valbenazine.
A poster on the study, “Low incidence of extrapyramidal symptoms in subjects with tardive dyskinesia receiving long-term valbenazine (NBI-98854) treatment,” was presented last month at the 21st International Congress of Parkinson’s Disease and Movement Disorders in Vancouver, BC.
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Valbenazine for Tardive Dyskinesia: A Case Study in Ensuring Rapid FDA Approval
