Valbenazine Shows Superior VMAT2 Occupancy: A New Era in Treating Movement Disorders?
Recent research is spotlighting valbenazine as a potentially more effective treatment option for movement disorders like tardive dyskinesia and Huntington’s disease-related chorea. A comparative study presented at the 64th Annual Meeting of the American College of Neuropsychopharmacology revealed that valbenazine achieves significantly higher occupancy of the VMAT2 receptor compared to deutetrabenazine XR.
Understanding VMAT2 and its Role in Movement
Both valbenazine and deutetrabenazine are VMAT2 inhibitors. VMAT2, or vesicular monoamine transporter 2, plays a crucial role in regulating dopamine levels in the brain. By blocking VMAT2, these medications reduce the amount of dopamine released, which can facilitate to alleviate involuntary movements. The effectiveness of these drugs hinges on how well they occupy the VMAT2 target.
Study Findings: Valbenazine Doubles Target Engagement
The study utilized PET imaging to assess VMAT2 occupancy after a single dose of either valbenazine (40mg or 80mg) or deutetrabenazine XR (24mg or 48mg). Results showed a least square mean VMAT2 occupancy of 76.5% with valbenazine, compared to 38.3% with deutetrabenazine XR. This represents a 38.2% difference (P = 0.0002), indicating a substantial advantage for valbenazine in binding to its target.
Further analysis, integrating pharmacokinetic models, confirmed this higher interaction with VMAT2 at all dosages, even at steady state. Valbenazine demonstrated 83% and 92% occupancy at 40mg and 80mg respectively, even as deutetrabenazine XR achieved 54% and 70% at 24mg and 48mg.
Beyond Motor Symptoms: Impact on Quality of Life
The benefits of valbenazine extend beyond symptom reduction. The KINECT PRO study, a phase 4 open-label study, assessed the impact of valbenazine on patient-reported outcomes in individuals with tardive dyskinesia. Significant improvements were observed as early as week four, with reductions in scores on the Tardive Dyskinesia Impact Scale (TDIS) ranging from -6.8 for mild cases to -8.9 for moderate/severe cases.
Improvements were too noted in the Sheehan Disability Scale (SDS), indicating enhanced functionality in social and family life, and in the EQ 5D 5L, a measure of overall health-related quality of life.
Expert Commentary and Future Implications
Sanjay Keswani, Chief Medical Officer of Neurocrine Biosciences, stated that the higher VMAT2 occupancy observed with valbenazine may contribute to the rapid and stable clinical efficacy seen in studies of tardive dyskinesia and Huntington’s disease-related chorea. This suggests that a stronger engagement with the target receptor could translate to more consistent and pronounced clinical benefits.
These findings reinforce valbenazine’s position as a highly effective VMAT2 inhibitor, with a superior target occupancy and a significant clinical impact on both motor symptoms and quality of life. The emerging evidence suggests an increasingly central role for the drug in managing tardive dyskinesia and related movement disorders.
Frequently Asked Questions
- What is VMAT2? VMAT2 is a protein that packages dopamine and other neurotransmitters for release in the brain.
- What is tardive dyskinesia? Tardive dyskinesia is a movement disorder characterized by involuntary movements, often affecting the face, tongue, and other body parts.
- How does valbenazine work? Valbenazine blocks VMAT2, reducing dopamine release and alleviating involuntary movements.
- Is valbenazine safe? Both valbenazine and deutetrabenazine were well-tolerated in the studies mentioned, with no new safety signals identified.
Did you know? The FDA has approved both valbenazine and deutetrabenazine for the treatment of tardive dyskinesia and Huntington’s disease-related chorea.
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