VMAT2 Inhibitor NBI-1065890 Heads to Phase 2 Study in Tardive Dyskinesia

In recent news, Neurocrine Biosciences has initiated a new phase 2 trial (NCT) testing its investigational NBI-1065890, a vesicular monoamine transporter 2 (VMAT2) inhibitor, as a treatment for adults with tardive dyskinesia (TD). The interventional study, expected to include 100 patients, is anticipated to conclude in early 2027.¹

This newly initiated study is a double-blind, randomized, placebo-controlled trial testing the efficacy, safety, and tolerability of NBI-1065890 against placebo for an 8-week treatment period. In the study, investigators will use change in Abnormal Involuntary Movement Scale (AIMS) dyskinesia score–sum of items 1-7–as the primary end point, with change in Clinical Global Impression-Improvement responder score as a secondary outcome.

“NBI-'890 is an internally discovered molecule with distinct physical and chemical properties that may allow it to benefit a broader range of patients with tardive dyskinesia,” Sanjay Keswani, MD, chief medical officer at Neurocrine, said in a statement.¹ “Advancing this program to a Phase 2 clinical study is key to our strategy to define the future of VMAT2 biology and deliver lasting impact for patients.”

READ MORE: Valbenazine Safe and Effective for Long-Term Treatment of Tardive Dyskinesia in Elders

NBI-1065890, an oral therapy, is believed to have a differentiated profile as other TD therapies, including a potentially longer-acting release. Neurocrine’s first VMAT2 inhibitor, valbenazine, was first approved in 2017 for TD, and later had its indication expanded in 2023 to include the treatment of chorea associated with Huntington disease (HD).

For eligibility, adults may have a medically confirmed DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder for at least 3 months before screening, along with a diagnosis of neuroleptic-induced TD for at least the same duration. Coming into the trial, participants are required to have moderate to severe TD, determined through a blinded external video review of the AIMS assessment. Specifically, patients needed an AIMS Item 8 score indicating overall abnormal movement severity and a dyskinesia total score of 6 or higher across AIMS Items 1 through 7.²

Patients are excluded from the study if they had comorbid parkinsonism, including drug-induced forms, or more than minimal extrapyramidal symptoms based on the Modified Simpson-Angus Scale. Additional exclusions included clinically significant akathisia, marked psychiatric symptom severity, or psychiatric hospitalization within the prior 6 months. Individuals with unstable medical conditions or chronic diseases, as well as those with any history of neuroleptic malignant syndrome, were also not eligible to participate.

Prior to this study, NBI-1065890 was tested in a phase 1 first-in-human trial of healthy volunteers. During that time, Neurocrine was also testing several other agents, such as NBI-1117570, NBI-1117567, NBI-1117569, and NBI-1065890, in early-stage studies.³

REFERENCES
1. Neurocrine Biosciences Initiates Phase 2 Clinical Study Evaluating NBI-1065890 in Adults with Tardive Dyskinesia. News release. January 26, 2026. Accessed January 29, 2026. https://neurocrine.gcs-web.com/news-releases/news-release-details/neurocrine-biosciences-initiates-phase-2-clinical-study-0
2. Efficacy, Safety, and Tolerability of NBI-1065890 Versus Placebo in Adults With Tardive Dyskinesia. Clinicaltrials.gov. Updated January 26, 2026. Accessed January 29, 2026. https://clinicaltrials.gov/study/NCT07365462
3. 2024 Annual Report. Neurocrine Biosciences. Accessed January 29, 2026. https://www.neurocrine.com/media/documents/NBIX_2024_Annual_Report_UgN6knI.pdf