Plasma kallikrein Inhibitors
4 drugsAbout Plasma kallikrein
Plasma kallikrein (KLKB1) is a serine protease in blood plasma involved in coagulation and inflammation via the kallikrein-kinin system. It influences vasodilation, inflammation, and blood pressure regulation.
Human genetic studies provide strong validation for plasma kallikrein as a therapeutic target (max score 0.89). Loss-of-function variants are associated with inherited prekallikrein deficiency (0.89), prekallikrein deficiency (0.82), and venous thromboembolism (0.79), suggesting activation may be beneficial.
Plasma kallikrein is targeted by four FDA-approved drugs: EKTERLY, TAKHZYRO, ORLADEYO, and KALBITOR. These include small molecules (2), a biologic (1), and a peptide (1), used in various therapeutic areas.
Plasma kallikrein Genetic Evidence Strong
Strong genetic evidence supports plasma kallikrein as a drug target, with a maximum score of 0.89.
The strong genetic support suggests a higher likelihood of clinical success for plasma kallikrein-targeting drugs.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in hematologic disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link KLKB1 to 20 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 KLKB1 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 Plasma kallikrein Drugs
Three companies have approved drugs targeting plasma kallikrein: KALVISTA, DYAX CORP., and BIOCRYST.
The presence of three companies indicates a moderately competitive landscape, suggesting potential entry barriers for new players.
Plasma kallikrein Drug Modality Landscape
Modalities
Routes of Administration
Plasma kallikrein is druggable by both biologics (2) and small molecules (2), indicating broad therapeutic accessibility.
Given the existing peptide and small molecule drugs, biologics targeting plasma kallikrein may represent a whitespace opportunity.
📈 Modality Evolution
Peptides pioneered Plasma kallikrein targeting (2009), with small molecules entering more recently (2020).
Plasma kallikrein Clinical Trials 19 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Plasma kallikrein. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 5 | 3 | 2 | 0 | 60% |
| Phase 2 | 6 | 3 | 3 | 0 | 50% |
| Phase 3 | 8 | 6 | 0 | 2 | 100% |
Top Sponsors
By Modality
Top Conditions
Plasma kallikrein Drug Approval Timeline (2009 - 2025)
The first drug was approved in 2009 (KALBITOR), with the most recent approval in 2025 (EKTERLY).
The 17-year span of approvals indicates sustained interest and potential for further development in this target area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 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: 9 (6 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 Plasma kallikrein. A trial counts if an approved drug acting on Plasma kallikrein 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.