48-Week Data Show Efficacy of Valbenazine in Patients With Tardive Dyskinesia and Schizophrenic, Mood Disorders

Key Takeaways

Valbenazine capsules led to remission in 59.2% of patients with tardive dyskinesia in the KINECT 4 trial.
The trial showed significant improvements in AIMS scores, with consistent remission rates across psychiatric diagnoses.
Valbenazine was well tolerated, with minimal clinically significant changes in psychiatric stability and vital signs.
Treatment-emergent adverse events included urinary tract infection and headache, occurring in at least 5% of patients.

About 59.2% of patients with tardive dyskinesia (TD) who completed the 48-week trial achieved remission.

Recent data from the KINECT 4 trial (NCT02405091) demonstrated the remission of tardive dyskinesia (TD) among the majority of patients who were treated with valbenazine capsules (Ingrezza; Neurocrine Biosciences) once per day.¹ These data were presented at the 2025 Psychiatry Update Conference, which was held in Chicago, Illinois, from March 20 to March 22.²

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TD is a movement disorder characterized by uncontrollable, abnormal, and repetitive movements of the face, torso, and/or other body parts, which may be disruptive and negatively impact patients. TD is estimated to affect at least 800,000 adults in the US and is often associated with taking certain antipsychotics, which help control dopamine receptors in the brain. Antipsychotic medications commonly prescribed to treat mental illnesses (eg, major depressive disorder, bipolar disorder, schizophrenia, and schizoaffective disorder) and other prescription medicines (eg, metoclopramide and prochlorperazine) used to treat gastrointestinal disorders are associated with TD. In patients with TD, these treatments are believed to result in irregular dopamine signaling in a region of the brain that controls movement. TD symptoms can be severe and are often persistent and irreversible.²

Valbenazine is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor that is FDA-approved for the treatment of adults with TD and the treatment of Huntington disease-associated chorea. It is available in a once-daily capsule that can be swallowed or sprinkled and consumed. It offers a therapeutic dose from day 1 with no required titration. Valbenazine works by selectively inhibiting VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic, serotonergic, adrenergic, histaminergic, or muscarinic receptors. The agent selectively and specifically targets VMAT2 to inhibit the release of dopamine, leading to fewer uncontrollable movements.²

The KINECT 4 trial is an open-label phase 3 study that assessed the safety and tolerability of valbenazine when treating 163 patients with moderate to severe TD and underlying schizophrenia, schizoaffective disorder, or mood disorder (eg, major depressive disorder and bipolar disorder). Patients received once-daily doses initiated as 40 mg per day, with escalations to 80 mg per day at week 4 based on effectiveness and tolerability.^1,2

The findings presented at the conference were 48-week data that featured data from 103 patients who reached the final visit (week 48) of the clinical trial. These patients were assessed a proposed threshold for remission of TD symptoms using the Abnormal Involuntary Movement Scale (AIMS), which was defined as an item score of 1 or lower (rating of “none” or “minimal”) in each of the 7 body regions (items 1-7). The percentage who met the threshold for remission was analyzed by dose (40 mg or 80 mg) and by psychiatric diagnosis, according to the investigators.^1,2

The majority (59.2%; n = 61) of participants who completed the study achieved remission, and this includes 58.6% (n = 17) of participants on the 40-mg dose and 59.5% (n = 44) of those on the 80-mg dose. Additionally, both doses demonstrated significant improvements in AIM total scores, with mean baseline scores of 12.4 and 15.1 decreasing to 2.1 and 2.5, respectively. Remission rates were consistent across all psychiatric diagnoses, with 57.7% (n = 41) of participants with schizophrenia or schizoaffective disorder and 62.5% (n = 20) of participants with mood disorders achieving remission.²

Further, patients experienced TD improvements during long-term treatment as shown by the mean change from baseline to week 48 in AIMS total score (sum of items 1-7) with 40 mg per day (-10.2) or 80 mg per day (-11.0). Additionally, valbenazine was generally well tolerated, which is consistent with prior research.²

About the Trial

Trial Name: Safety and Tolerability Study of NBI-98854 for the Treatment of Tardive Dyskinesia (Kinect 4)

ClinicalTrials.gov ID: NCT02405091

Sponsor: Neurocrine Biosciences

Completion Date: March 2017

After week 4, treatment-emergent adverse events that occurred in at least 5% of patients across both dose groups were urinary tract infection (8.5%) and headache (5.2%). The changes from baseline observed in psychiatric stability, vital signs, electrocardiogram parameters, and laboratory test values were generally small and not considered clinically significant, according to the investigators.²

"These findings further establish [valbenazine] as a highly effective long-term treatment option for individuals living with TD, regardless of their underlying psychiatric condition, including schizophrenia, schizoaffective disorder, or mood disorder," Eiry W. Roberts, MD, chief medical officer of Neurocrine Biosciences, said in a news release. "The significant improvements observed in AIMS score and the high remission rates highlight the efficacy of [valbenazine], at even the lowest dose."¹

REFERENCES

1. Safety and Tolerability Study of NBI-98854 for the Treatment of Tardive Dyskinesia (Kinect 4). ClinicalTrials.gov identifier: NCT02405091. Updated November 30, 2018. Accessed March 26, 2025. https://clinicaltrials.gov/study/NCT02405091

2. PR Newswire. Neurocrine Biosciences Presents 48-Week Remission Data on Treatment of Tardive Dyskinesia With INGREZZA® (valbenazine) Capsules. News release. March 20, 2025. Accessed March 26, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-48-week-remission-data-on-treatment-of-tardive-dyskinesia-with-ingrezza-valbenazine-capsules-302406507.html