Phase 2 Study Initiated for NBI-1065890 to Treat Tardive Dyskinesia

Neurocrine Biosciences announced initiation of a phase 2 study for NBI-1065890 in adults with tardive dyskinesia.¹ The study will assess safety, efficacy, and tolerability of the drug, focusing on change in abnormal movement. NBI-1065890 may offer a longer-acting treatment option for tardive dyskinesia, the company noted.

"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," said Sanjay Keswani, MD, chief medical officer of Neurocrine Biosciences.¹ Keswani added that "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."

The phase 2 trial will be randomized, double-blind, and placebo-controlled, with an enrollment goal of around 100 participants ages 18 to 75. To measure efficacy, the study’s primary endpoint will be change from baseline in the Abnormal Involuntary Movement Scale dyskinesia total score at week 8.² Secondary endpoints include percentage of participants who are responders on the Clinical Global Impression-Improvement assessment at week 8.

Inclusion criteria address psychiatric diagnosis and tardive dyskinesia diagnosis. Patients must have a confirmed diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder as defined by the DSM-5. A confirmed diagnosis of neuroleptic-induced tardive dyskinesia (as defined by DSM-5) at least 3 months prior to screening is also required. Moderate to severe tardive dyskinesia is required, as assessed via video by a blinded examiner. Exclusion criteria include comorbid parkinsonism or above minimal extrapyramidal symptoms and prior hospitalization for schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder within 6 months of screening. An unstable medical condition or chronic disease, a known history of neuroepileptic malignant syndrome, or above established threshold scores on the Barnes Akathisia Rating Scale and Brief Psychiatric Rating Scale.

NBI-1065890 is an oral inhibitor of vesicular monoamine transporter 2 (VMAT2) currently in clinical development for treatment of tardive dyskinesia. VMAT2 inhibitors are thought to provide benefit for patients with tardive dyskinesia, other hyperkinetic movement disorders, and potentially other central nervous system disorders with related dopaminergic signaling dysregulation. This type of drug can reduce dopamine levels by depleting monoamine neurotransmitters presynaptically, and the reduction is thought to benefit movement disorders like tardive dyskinesia.³ With tardive dyskinesia, VMAT2 inhibitors can reduce amounts of dopamine in the synapse, which can mitigate symptoms related to upregulation of dopamine receptors and dopaminergic hypersensitivity. Another VMAT2 inhibitor, valbenazine, was approved by the US Food and Drug Administration in 2017 for treatment of tardive dyskinesia. The drug was later approved for chorea associated with Huntington disease in 2023.

Primary completion of this phase 2 study is expected in February 2027, with full completion estimated in March 2027.

References

1. Neurocrine Biosciences initiates phase 2 clinical study evaluating NBI-1065890 in adults with tardive dyskinesia. Press release. January 26, 2026. Accessed January 26, 2026. https://www.prnewswire.com/news-releases/neurocrine-biosciences-initiates-phase-2-clinical-study-evaluating-nbi-1065890-in-adults-with-tardive-dyskinesia-302669338.html

2. Efficacy, safety, and tolerability of NBI-1065890 versus placebo in adults with tardive dyskinesia. ClinicalTrials.gov. January 26, 2026. Accessed January 6, 2026. https://clinicaltrials.gov/study/NCT07365462?term=NBI-1065890-TD2033&rank=1

3. What are VMAT2 inhibitors and how do they work? Synapse. June 21, 2024. Accessed January 26, 2026. https://synapse.patsnap.com/article/what-are-vmat2-inhibitors-and-how-do-they-work