Aromatase Inhibitors
5 drugsAbout Aromatase
Aromatase (estrogen synthetase) is an enzyme that catalyzes the conversion of androgens to estrogens, a critical step in estrogen biosynthesis. Its enzymatic activity makes it a significant drug target, particularly in oncology, as inhibiting aromatase reduces estrogen production.
Human genetics provide strong support for targeting aromatase (max score 0.87), with loss-of-function variants linked to aromatase deficiency (0.87) and excess syndrome (0.77). Activation is likely beneficial, suggesting potential therapeutic strategies.
Aromatase is targeted by 5 FDA-approved small molecule drugs, including KISQALI FEMARA CO-PACK, AROMASIN, and ARIMIDEX. Four drugs are used in oncology, while one addresses a different therapeutic area.
Aromatase Genetic Evidence Strong
Aromatase has strong genetic support with a maximum score of 0.87 and 29 diseases showing genetic evidence.
Strong genetic support suggests that clinical trials targeting aromatase have a higher likelihood of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in pregnancy or perinatal disease, genetic, familial or congenital disease, endocrine system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link CYP19A1 to 29 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for CYP19A1 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 Aromatase Drugs
Four companies have approved drugs targeting aromatase, including Teva, Pfizer, ANI PHARMS, and Novartis.
The presence of multiple established players indicates a moderately competitive market with potential entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| ARIMIDEX | AstraZeneca | 1995 | 1 |
| KISQALI FEMARA CO-PACK (COPACKAGED) | Novartis | 2017 | - |
Aromatase Drug Modality Landscape
Modalities
Routes of Administration
Aromatase is amenable to small molecule drugs, with oral options available for convenient dosing.
The absence of other modalities like antibodies or fusion proteins represents a potential whitespace opportunity.
Aromatase Clinical Trials 551 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Aromatase. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 123 | 70 | 18 | 35 | 80% |
| Phase 2 | 274 | 130 | 46 | 97 | 74% |
| Phase 3 | 112 | 38 | 13 | 60 | 75% |
| Phase 4 | 42 | 25 | 9 | 8 | 74% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved Aromatase drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Aromatase. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Aromatase Drug Approval Timeline (1995 - 2017)
The first aromatase inhibitor, ARIMIDEX, was approved in 1995, and the most recent, KISQALI FEMARA CO-PACK, in 2017.
The 23-year span between approvals suggests a mature market with potentially slowing innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 263 (58 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 Aromatase. A trial counts if an approved drug acting on Aromatase 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.