VMAT2 Inhibitors
6 drugsAbout VMAT2
VMAT2 (Vesicular Monoamine Transporter 2) transports dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles within the CNS. This packaging regulates neurotransmitter release and neuronal signaling, making it crucial for brain function.
VMAT2 is a strong therapeutic target with genetic support (max score 0.79) linking it to diseases like infantile dystonia-parkinsonism. Loss-of-function variants increase risk, suggesting activation strategies may be beneficial.
Six FDA-approved small molecule drugs target VMAT2, including AUSTEDO and INGREZZA, for CNS disorders. These drugs from Teva, NEUROCRINE, and BAUSCH highlight VMAT2's therapeutic potential.
VMAT2 Genetic Evidence Strong
VMAT2 has strong genetic support with a max score of 0.79 linking it to infantile dystonia-parkinsonism.
The strong genetic support suggests a higher probability of clinical success for VMAT2-targeting drugs.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
9 totalGWAS and other genetic studies link SLC18A2 to 9 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 1 strong
max H4: 0.92eQTL/pQTL signals for SLC18A2 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top VMAT2 Drugs
Teva, NEUROCRINE, and BAUSCH are the key players in the VMAT2 drug market.
The concentrated market suggests high barriers to entry for new companies targeting VMAT2.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| AUSTEDO XR | Teva | 2023 | 3 |
| INGREZZA | NEUROCRINE | 2017 | 2 |
| TETRABENAZINE | BIONPHARMA | 2015 | 1 |
VMAT2 Drug Modality Landscape
Modalities
Routes of Administration
VMAT2 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or gene therapies could provide a competitive advantage.
VMAT2 Clinical Trials 30 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on VMAT2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 5 | 3 | 2 | 0 | 60% |
| Phase 2 | 8 | 3 | 2 | 3 | 60% |
| Phase 3 | 9 | 6 | 2 | 1 | 75% |
| Phase 4 | 8 | 6 | 0 | 2 | 100% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
VMAT2 Drug Approval Timeline (2008 - 2024)
VMAT2 has seen approvals spanning 17 years, from 2008 (XENAZINE) to 2024 (INGREZZA SPRINKLE).
The recent approval of INGREZZA SPRINKLE suggests continued interest and potential in VMAT2-targeted therapies.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 6 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 6-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 15 (4 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on VMAT2. A trial counts if an approved drug acting on VMAT2 is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.