COMT Inhibitors
4 drugsAbout COMT
Catechol-O-methyltransferase (COMT) is an enzyme that degrades catecholamines like dopamine, epinephrine, and norepinephrine, influencing various physiological processes by modifying these neurotransmitters.
COMT is a therapeutic target with strong genetic support (max score 0.79) linking it to 17 diseases including hair color (0.79), internet addiction (0.59) and type 2 diabetes (0.58). Strong eQTL/pQTL signals further support COMT's role in disease.
Four FDA-approved drugs, including ENTACAPONE (COMTAN), TASMAR, and ONGENTYS, inhibit COMT activity, all are small molecules. Three drugs target CNS conditions, while one addresses a different therapeutic area.
COMT Genetic Evidence Strong
COMT has strong genetic support with a max score of 0.79 linked to hair color.
The strong genetic support suggests a higher likelihood of success in clinical trials targeting genetically validated indications.
Evidence Across Diseases
17 totalGWAS and other genetic studies link COMT to 17 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for COMT 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 COMT Drugs
Four companies, including Sun Pharma and ORION PHARMA, have approved COMT-targeting drugs.
The presence of multiple players suggests a moderately competitive market, requiring a differentiated approach for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| ENTACAPONE | Aurobindo Pharma | 2012 | 1 |
COMT Drug Modality Landscape
Modalities
Routes of Administration
COMT is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or PROTACs could provide a competitive advantage in modulating COMT activity.
COMT Clinical Trials 43 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on COMT. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 19 | 16 | 1 | 2 | 94% |
| Phase 2 | 12 | 11 | 1 | 0 | 92% |
| Phase 3 | 4 | 3 | 0 | 1 | 100% |
| Phase 4 | 8 | 5 | 3 | 0 | 63% |
Top Sponsors
By Modality
Top Conditions
COMT Drug Approval Timeline (1999 - 2020)
The first COMT drug was approved in 1998, with the most recent approval in 2020, spanning 23 years.
The recent approval suggests continued interest in COMT as a target, but market saturation may require novel strategies.
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Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 24 (8 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 COMT. A trial counts if an approved drug acting on COMT 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.