New Head-to-Head Data Shows Higher VMAT2 Target Occupancy for Ingrezza Compared With Austedo XR

Neurocrine Biosciences today announced the presentation of the first head-to-head data comparing vesicular monoamine transporter 2 (VMAT2) target occupancy between valbenazine (Ingrezza) capsules and deutetrabenazine (Austedo XR) at therapeutic doses. Results from the study confirmed that both compounds engage VMAT2; however, Ingrezza demonstrated significantly higher VMAT2 target occupancy and greater potency.¹

"In this head-to-head assessment, Ingrezza demonstrated approximately 2-fold higher target occupancy compared with Austedo XR at therapeutic doses," said Sanjay Keswani, MD, the chief medical officer of 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 disease chorea clinical trials."

VMAT2 inhibition is an established target for treatment of hyperkinetic movement disorders, such as tardive dyskinesia (TD) and Huntington 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.

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 8 participants, each completing 4 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. These data are consistent with our integrated understanding of the TO of Ingrezza and drug exposure concentrations observed from Ingrezza in pivotal clinical trials. 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.

These findings were presented at the American College of Neuropsychopharmacology 64th Annual Meeting on January 12-15 in the Bahamas.

A narrative review paper from November 2025 also examined the differences between Ingrezza and deutetrabenazine, ultimately emphasizing the distinct pharmacologic, dosing, and clinical profiles of the 2 drugs.^2,3 The review presented results from double-blind, placebo-controlled clinical trials, post-hoc analyses, and long-term studies for both VMAT2 inhibitors. Ingrezza was noted to have unique attributes of selectivity to VMAT2, demonstrated therapeutic response at 40 mg (the lowest available dose), and data collected across a range of patient populations. Ingrezza and deutetrabenazine were noted to have key differences. Both medications target VMAT2 receptors, but Ingrezza was found to work with a single metabolite with high affinity for VMAT2 and had no off-target receptor activity.

References

1. Neurocrine Biosciences presents head-to-head INGREZZA® (valbenazine) capsules data demonstrating Higher VMAT2 target occupancy compared to AUSTEDO XR. News release. January 15, 2026. Accessed January 15, 2026. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-head-to-head-ingrezza-valbenazine-capsules-data-demonstrating-higher-vmat2-target-occupancy-compared-to-austedo-xr-302661800.html

2. Patel AR, Hauser RA, Citrome L, et al. VMAT2 inhibitors for the treatment of tardive dyskinesia: a narrative review. CNS Spectrums. 2025;30(1):e90.

3. Walters J. New review on VMAT2 inhibitors and Ingrezza for treatment of tardive dyskinesia. Psychiatric Times. November 20, 2025. https://www.psychiatrictimes.com/view/new-review-on-vmat2-inhibitors-and-ingrezza-for-treatment-of-tardive-dyskinesia