ETA Inhibitors
8 drugsAbout ETA
ETA, also known as endothelin receptor type A (EDNRA), regulates blood vessel constriction and cell growth. As a key drug target in the cardiovascular system, it modulates vascular tone and influences cellular proliferation pathways.
Human genetic studies provide strong validation for ETA as a therapeutic target, with variants linked to coronary artery disease (score 0.89) and angina pectoris (score 0.86). These findings support therapeutic interventions modulating ETA activity.
ETA is targeted by 4 FDA-approved small molecule drugs, including TRACLEER, OPSUMIT, TRYVIO and OPSYNVI, all indicated for cardiovascular conditions. Actelion and Idorsia are the key players in this space.
ETA Genetic Evidence Strong
ETA has strong genetic support with a max score of 0.89 linking it to coronary artery disease.
Strong genetic support suggests a higher probability of clinical success for ETA-targeting drugs.
Evidence Across Diseases
20 totalGWAS and other genetic studies link EDNRA to 48 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for EDNRA 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 ETA Drugs
Actelion and Idorsia are the only two companies with approved ETA-targeting drugs.
The concentrated competitive landscape indicates high barriers to entry for new companies.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| MACITENTAN | AMNEAL | 2021 | 1 |
| OPSYNVI | ACTELION | 2024 | 1 |
| TRYVIO | IDORSIA | 2024 | 1 |
| LETAIRIS | Gilead Sciences | 2007 | 1 |
| VANRAFIA | Novartis | 2025 | 1 |
ETA Drug Modality Landscape
Modalities
Routes of Administration
ETA is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape suggests an opportunity to explore alternative modalities like antibodies or peptides.
ETA Clinical Trials 163 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on ETA. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 43 | 38 | 3 | 1 | 93% |
| Phase 2 | 46 | 27 | 11 | 8 | 71% |
| Phase 3 | 51 | 27 | 17 | 7 | 61% |
| Phase 4 | 23 | 13 | 7 | 3 | 65% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved ETA drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting ETA. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
ETA Drug Approval Timeline (2001 - 2025)
The first ETA-targeting drug was approved in 2001, with the most recent approval in 2024.
The 24-year span suggests a mature market with potential for incremental innovation rather than disruptive breakthroughs.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 companies competing
- • Market share by company
Full Drug Portfolio
- • All 8 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 8-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 66 (20 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 ETA. A trial counts if an approved drug acting on ETA 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.