Trials of valbenazine for TD do not find that the treatment adds to cardiovascular disease risks associated with schizophrenia or the cardiovascular complications of antipsychotics.
Analysis of data from a trio of 6-week trials with valbenazine (Ingrezza) did not find that the tardive dyskinesia (TD) therapy adds to the cardiovascular disease (CVD) risks associated with schizophrenia or the cardiovascular complications of antipsychotic drugs.
Dao Thai-Cuarto, PharmD, MBA, director of Clinical Drug Safety at Neurocrine Biosciences, and researchers confirmed that valbenazine had minimal cardiovascular effects in patients with TD who had a concurrent psychiatric disorder, “the majority of whom were taking concomitant antipsychotic or antidepressant medications.”
The results are particularly welcome as evidence of heightened risk of CVD in patients with schizophrenia and adverse cardiovascular effects from antipsychotic drugs continues to build.
In May, investigators on a study of risk factors for early circulatory mortality in patients with schizophrenia pointed out that CVD accounts for up to 50% of cases of early mortality in schizophrenia.
In June, an investigation into possible mechanisms underlying cardiovascular complications from antipsychotic medication confirmed their link to elevated lipoprotein-associated phospholipse A2 levels, and suggests this could contribute to CVD.
To ascertain whether using valbenazine to treat TD contributes to the risk of cardiovascular disease in this at-risk patient population, Thai-Cuarto and colleagues analyzed the pooled data from 3 randomized, double-blind, placebo controlled trials. The study cohorts were comprised of patients with schizophrenia or schizoaffective disorder or mood disorder, who were receiving pharmacotherapy for their symptoms.
Antipsychotic medication was the most common concurrent medication class (84%), followed by antidepressant (63.8%) and anxiolytic (28.8%). The researchers noted that most patients (74.3%) were taking medications with known potential to increase the QT interval, and were allowed to participate after medical review.
Of the 400 participants in the pooled safety population, 388 (97%) had some reported medical history. A diagnosis of a specific cardiac disorder was found in 47 (11.8%) of the participants and hypertension was documented in 53.3%. The mean age was 55.8 years, and the mean age of TD diagnosis was 48.2 years. More than half of the study cohorts were male (57.3%).
Although the researchers noted that the placebo-controlled data were only accumulated for 6 weeks, they found no statistically significant difference between valbenazine and placebo on adverse changes in vital signs or electrocardiogram parameters.
There were also no unexpected cardiovascular effects in a longer extension period in which participants received up to 48 weeks of treatment with valbenazine.
There was also no statistically significant difference between study drug and placebo in the treatment-emergent adverse events. Five cardiac-related events occurred during the 6-week study period, each reported in 1 participant: chest pain, bradycardia, increased blood pressure, a fatal myocardial infarction (MI) in a 73-year-old male with multiple cardiac risk factors on the study drug which was deemed unrelated, and a fatal MI in a participant receiving placebo.
Thai-Cuarto and colleagues anticipate that the cardiovascular safety profile of valbenazine will become clearer with post-marketing surveillance, and with 2 longer studies that involve different populations and have 12 and 18 months of follow-up, respectively.
"The cardiovascular effects of valbenazine will be evaluated in planned and ongoing studies of other movement disorders, eg Tourette syndrome," researchers wrote.
The study, "Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials," was published online in Drug Safety.