Factor IIa Inhibitors
12 drugsAbout Factor IIa
Factor IIa, also known as prothrombinase, is a serine protease essential for the blood coagulation cascade. It converts fibrinogen to fibrin, forming blood clots and playing a vital role in hemostasis and thrombosis.
Human genetic studies strongly validate Factor IIa as a therapeutic target, with variants linked to congenital prothrombin deficiency (score 0.94), prothrombin deficiency (0.93), and deep vein thrombosis (0.91). Loss-of-function variants are associated with increased risk of deficiency but protect against deep vein thrombosis, suggesting potential for activation-based therapies.
Factor IIa is targeted by 12 FDA-approved drugs, including heparin sodium formulations and Defencath, all of which are small molecules. These drugs are developed by companies like Pfizer, Fresenius Kabi, Baxter and CORMEDIX, primarily for cardiovascular indications.
Factor IIa Genetic Evidence Strong
Strong genetic evidence supports Factor IIa's role in coagulation-related diseases, with a maximum score of 0.94.
Strong genetic support increases confidence in targeting Factor IIa for coagulation disorders.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 67% directional consistency across 3 traits
- • Strong signal in hematologic disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
67% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link F2 to 42 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 F2 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 Factor IIa Drugs
The Factor IIa drug market involves four main companies, including Pfizer and Fresenius Kabi.
The concentrated market suggests high barriers to entry for new competitors.
Factor IIa Drug Modality Landscape
Modalities
Routes of Administration
Factor IIa is druggable by small molecules, though no oral formulations are currently approved.
The absence of other modalities like antibodies or biologics represents a whitespace opportunity.
Factor IIa Clinical Trials 172 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Factor IIa. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 24 | 18 | 4 | 2 | 82% |
| Phase 2 | 43 | 19 | 15 | 9 | 56% |
| Phase 3 | 45 | 24 | 11 | 10 | 69% |
| Phase 4 | 60 | 39 | 9 | 11 | 81% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Factor IIa Drug Approval Timeline (1972 - 2023)
Venous Thrombosis
Venous Thrombosis
HEPARIN SODIUM IN SODIUM CHLORIDE INJECTION is indicated ...
Venous Thrombosis
Venous Thrombosis
Venous Thrombosis
The first Factor IIa-targeting drug was approved in 1972, with the most recent in 2023.
The 52-year span indicates a mature market with potential for incremental innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 12 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 12-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 142 (29 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 Factor IIa. A trial counts if an approved drug acting on Factor IIa 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.