INGREZZA Shows Nearly Two-Fold Higher VMAT2 Target Occupancy vs AUSTEDO XR

Neurocrine Biosciences has presented the first head-to-head data comparing VMAT2 target occupancy between INGREZZA® (valbenazine) and AUSTEDO XR® (deutetrabenazine) at therapeutic doses. The results show a clear difference in target engagement.

INGREZZA achieved nearly double the VMAT2 occupancy, a marker linked to drug response in involuntary movement disorders.

Why VMAT2 Occupancy Matters?

VMAT2 inhibition is a validated mechanism in:

• Tardive dyskinesia (TD)
• Huntington’s disease (HD) chorea

Higher VMAT2 occupancy indicates stronger target engagement. This reduces excessive dopamine signaling that drives involuntary movements.

Head-to-Head Study Highlights

The study used PET imaging to measure VMAT2 occupancy after a single dose.

Key details:

• 8 participants
• Four PET scans per participant
• Therapeutic doses only

Primary Findings

• INGREZZA: ~76.5% VMAT2 occupancy
• AUSTEDO XR: ~38.3% VMAT2 occupancy

That is an approximate two-fold difference.

Estimated Steady-State VMAT2 Occupancy
 

Modeling based on pharmacokinetic exposure and EC50 values supported superior and sustained VMAT2 engagement with INGREZZA.

What Drives the Difference?

Neurocrine attributes the higher occupancy to pharmacology.

• INGREZZA produces a single high-affinity active metabolite
• AUSTEDO XR generates multiple metabolites, including some with lower VMAT2 affinity

This may explain differences in potency and clinical performance.

Clinical Relevance

According to Neurocrine Biosciences:

• Higher VMAT2 occupancy may support earlier and sustained efficacy
• Findings align with outcomes from multiple TD and HD chorea trials
• Both treatments were generally well tolerated, with safety profiles consistent with prior data

INGREZZA at a Glance

• FDA-approved for tardive dyskinesia and HD chorea
• Once-daily dosing, no titration required
• Available in capsule and sprinkle formulations
• Designed to selectively inhibit VMAT2, with minimal off-target activity

Bigger Picture

This head-to-head PET study adds mechanistic clarity to differences among VMAT2 inhibitors.

For clinicians and researchers, the data reinforce how target engagement, not just dose, shapes clinical outcomes in movement disorders.

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