SAN DIEGO -- Valbenazine (Ingrezza) appears safe and well-tolerated over a year of treatment, researchers reported here.
In a pooled analysis of data from 3 studies, about two-thirds of patients experienced treatment-emergent adverse events (TEAEs), but only about 15% discontinued the drug due to adverse events, Christopher O'Brien, MD, chief medical officer at Neurocrine Biosciences, reported during a poster session at the American Psychiatric Association meeting.
Among those with schizophrenia, the three most common TEAEs were urinary tract infection (6.1%), headache (5.8%), and somnolence (5.2%). Among those with mood disorders, the three most common TEAEs were headache (12.4%), urinary tract infection (10.7%), and somnolence (9.1%), O'Brien reported.
"Valbenazine appeared to be well tolerated in adults with tardive dyskinesia who received up to 48 weeks of treatment," O'Brien said. "In addition to long-term efficacy results, which were presented separately, these results suggest that valbenazine may be appropriate for the long-term management of tardive dyskinesia regardless of underlying psychiatric diagnosis."
The involuntary movements characterizing tardive dyskinesia (TD) can be caused by taking medications (dopamine receptor blocking agents, including antipsychotics) for schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was recently approved by the FDA to treat this side effect.
Valbenazine works by inhibiting the vesicular monoamine transporter 2 (VMAT2), modulating dopaminergic neurotransmission by reducing synaptic dopamine levels, thereby improving symptoms of tardive dyskinesia.
For this analysis, the team looked at data from three phase III trials: KINECT, KINECT 3, and KINECT 4, in which dosages ranged from 40 mg to 100 mg per day. The total number of patients included in the analysis was 430, and patients were observed for up to 48 weeks.
Patients required a diagnosis of tardive dyskinesia for ≥3 months prior to screening, as well as a DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or mood disorder. Participants needed a stable psychiatric status (Brief Psychiatric Rating Scale score <50 at screening). They also had moderate or severe tardive dyskinesia, as qualitatively assessed by a blinded, external reviewer using an Abnormal Involuntary Movement Scale (AIMS) video.
Exclusion of patients included those with an active, clinically significant, and unstable medical conditions within 1 month prior to screening. Patients were also excluded if they had comorbid movement disorder (e.g., parkinsonism, akathisia, truncal dystonia) that was more prominent than tardive diskynesia. Finally, patients at significant risk for active suicidal ideation, suicidal behavior, or violent behavior were not included.
A lifetime history of suicidal ideation or behavior was reported in 39.8% of all participants. Nonetheless, long-term valbenazine treatment did not appear to increase suicidality, based on spontaneous TEAE reporting or Calgary Depression Scale for Schizophrenia (C-SSRS) responses, O'Brien said.
Stable doses of concomitant medications to treat the psychiatric disorders were permitted throughout the studies. Approximately 85% of participants were receiving ≥1 concomitant antipsychotic medication throughout the trial. However, there was no clinical evidence of drug interaction toxicities, he noted.
No notable electrocardiogram (ECG) changes occurred, including the 81% of participants who were taking concomitant medications with a known potential to prolong QT. Furthermore, mean changes in laboratory parameters, vital signs, ECG, and extrapyramidal symptoms (EPS) scales were generally minimal and not clinically significant, O'Brien said.
Disclosures
O'Brien is an employee of Neurocrine Biosciences.
Primary Source
American Psychiatric Association
Josiassen RC, et al "Long-term safety and tolerability of valbenazine in subjects with tardive dyskinesia and a diagnosis of schizophrenia or mood disorders" APA 2017.