Neurocrine Biosciences Presents Head-to-Head Data Showing INGREZZA® (valbenazine) Capsules Achieve Higher VMAT2 Target Occupancy Than AUSTEDO XR
Neurocrine Biosciences, Inc. today announced the presentation of the first head-to-head data comparing vesicular monoamine transporter 2 (VMAT2) target occupancy between INGREZZA® (valbenazine) capsules and AUSTEDO XR (deutetrabenazine) at therapeutic doses. Results from the study confirmed that both compounds engage VMAT2; however, INGREZZA demonstrated significantly higher VMAT2 target occupancy and greater potency. Findings were presented at the American College of Neuropsychopharmacology 64th Annual Meeting taking place January 12-15 in the Bahamas.
VMAT2 inhibition is an established target for treatment of hyperkinetic movement disorders, such as tardive dyskinesia (TD) and Huntington’s disease (HD) chorea. VMAT2 target occupancy (TO) is a key measurement thought to be associated with the level of drug response in these conditions. Higher VMAT2 occupancy indicates greater engagement of the target, and inhibition of VMAT2 lowers excessive dopamine transmission associated with involuntary movements.
“In this head-to-head assessment, INGREZZA demonstrated approximately two-fold higher target occupancy compared with AUSTEDO XR at therapeutic doses,” said Sanjay Keswani, M.D., Chief Medical Officer, Neurocrine Biosciences. “The significantly higher VMAT2 occupancy observed with INGREZZA adds to the already established differences between VMAT2 inhibitors in pharmacologic and clinical profiles. The high occupancy of INGREZZA may contribute to the robust early and sustained clinical efficacy consistently demonstrated in multiple tardive dyskinesia and Huntington’s disease chorea clinical trials.”
The study used positron emission tomography (PET) imaging to evaluate VMAT2 TO following single doses of either INGREZZA (40 mg or 80 mg) or AUSTEDO XR (24 mg or 48 mg) in eight participants, each completing four PET visits. Using a linear mixed-effects model, the primary TO analysis demonstrated a least squares mean VMAT2 occupancy of approximately 76.5% for INGREZZA compared with approximately 38.3% for AUSTEDO XR at therapeutic doses.
Pharmacokinetic exposure modeling and calculated half-maximal effective concentration (EC50) values enabled estimates of steady-state TO with superior VMAT2 engagement at therapeutic doses of INGREZZA compared to AUSTEDO XR. Findings are depicted in the table below:
| VMAT2 Inhibitor | Dose (mg) | Estimated Steady-State VMAT2 Occupancy |
| INGREZZA | 40 | 83 % |
| 80 | 92 % | |
| AUSTEDO XR | 24 | 54 % |
| 48 | 70 % |
These data are consistent with our integrated understanding of the TO of INGREZZA and drug exposure concentrations observed from INGREZZA in pivotal clinical trials.1,2 The superior target engagement observed with INGREZZA may be related to its single high affinity metabolite, compared with AUSTEDO XR, which generates multiple metabolites, including those with lower VMAT2 affinity.
All doses of INGREZZA and AUSTEDO XR were generally well tolerated and consistent with the known safety profile of each compound.
Additional presentations at the 2026 American College of Neuropsychopharmacology Annual Meeting:
- Once-Daily Valbenazine Improves Patient-Reported Quality of Life in Patients From KINECT-PRO™ Who Met a Remission Threshold for Tardive Dyskinesia
- Potential Change in Disease Burden with Valbenazine in Adults with Huntington’s Disease: Post Hoc Analysis of Cognitive- and Emotional-Related HD-HI Items in the KINECT®-HD Trial
- Osavampator (NBI-1065845/TAK-653) Demonstrates Statistically Significant and Clinically Meaningful Improvements in Depression Severity and is Well Tolerated in Adults with Major Depressive Disorder: Phase 2 SAVITRI Results
About Tardive Dyskinesia
Tardive dyskinesia (TD) is a movement disorder that is characterized by uncontrolled, abnormal and repetitive movements of the face, torso and/or other body parts, which may be disruptive and negatively impact patients. The condition is associated with taking certain kinds of mental health medicines (antipsychotics) that help control dopamine receptors in the brain. Taking antipsychotics commonly prescribed to treat mental illnesses such as major depressive disorder, bipolar disorder, schizophrenia and schizoaffective disorder and other prescription medicines (metoclopramide and prochlorperazine) used to treat gastrointestinal disorders are associated with TD.
In patients with TD, these treatments are thought to result in irregular dopamine signaling in a region of the brain that controls movement. The symptoms of TD can be mild to severe and are often persistent and irreversible. TD is estimated to affect at least 800,000 adults in the U.S.
About Chorea Associated with Huntington’s Disease
Huntington’s disease (HD) is a hereditary progressive neurodegenerative disorder in which the loss of certain neurons within the brain causes motor, cognitive and psychiatric symptoms. Symptoms generally appear between the ages of 30 and 50 years and worsen over a 10- to 25-year period. Most people with HD experience chorea, an abnormal involuntary movement disorder, characterized by irregular and unpredictable movements. Chorea can affect various body parts and interfere with motor coordination, gait, swallowing and speech. HD is estimated to affect approximately 41,000 adults in the U.S., with more than 200,000 at risk of inheriting the disease.
About INGREZZA® (valbenazine) Capsules and INGREZZA® SPRINKLE (valbenazine) Capsules
INGREZZA is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington’s disease (HD). Only INGREZZA offers a therapeutic dose from day one with no required titration.
INGREZZA, developed by Neurocrine Biosciences, selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic or muscarinic receptors. While the specific way INGREZZA works to treat TD and HD chorea is not fully understood, INGREZZA is unique in that it selectively and specifically targets VMAT2 to inhibit the release of dopamine, a chemical in the brain that helps control movement. INGREZZA is believed to reduce extra dopamine signaling, which may lead to fewer uncontrollable movements.
INGREZZA is studied across the widest range of patients. It is always one capsule, once daily and can be taken together with most stable mental health regimens such as antipsychotics or antidepressants. Only INGREZZA offers the benefit of a sprinkle formulation, INGREZZA SPRINKLE, for those who experience dysphagia, have difficulty swallowing or prefer not to swallow a pill. INGREZZA and INGREZZA SPRINKLE dosages approved for use are 40 mg, 60 mg and 80 mg capsules.
Source Link: https://neurocrine.gcs-web.com/
