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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Autonomic Failure with only 1 trials.
Human 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 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 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.
Clinical Trials 69 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 28 | 25 | 1 | 2 | 96% |
| Phase 2 | 19 | 12 | 1 | 6 | 92% |
| Phase 3 | 8 | 6 | 0 | 2 | 100% |
| Phase 4 | 14 | 9 | 4 | 0 | 69% |
Top Sponsors
By Modality
Top Conditions
Drug Approval Timeline (1998 - 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.
Pro Intelligence Preview
Deep insights for drug target analysis
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
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 37 clinical trials targeting COMT.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities