VEGFR-3 Inhibitors
16 drugsAbout VEGFR-3
Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) is a receptor tyrosine kinase crucial for lymphangiogenesis. It regulates the formation of lymphatic vessels and has emerged as a significant target in oncology and other therapeutic areas.
Human genetic studies provide strong validation for VEGFR-3 as a therapeutic target (max score 0.95). Loss-of-function variants are associated with lymphatic malformation 1 (score 0.95), congenital heart defects (0.89), and Milroy disease (0.85), suggesting activation may be beneficial.
VEGFR-3 is targeted by 10 FDA-approved small molecule drugs, including CABOMETYX, SORAFENIB TOSYLATE, and INLYTA. These drugs are developed by 10 companies, including Viatris, NOVUGEN, and EXELIXIS, for oncology (4 drugs) and other indications (6 drugs).
VEGFR-3 Genetic Evidence Strong
VEGFR-3 has strong genetic support with a max score of 0.95 linked to lymphatic malformation 1.
Strong genetic support suggests that VEGFR-3 activators have a higher probability of clinical success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in cardiovascular disease, genetic, familial or congenital disease, hematologic disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
11 totalGWAS and other genetic studies link FLT4 to 11 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 FLT4 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 VEGFR-3 Drugs
Ten companies have approved VEGFR-3 drugs, with Viatris, NOVUGEN, and EXELIXIS leading.
The presence of 10 companies indicates moderate competition, but also potential for partnerships.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| RETEVMO | Eli Lilly | 2020 | 4 |
| STIVARGA | Bayer | 2012 | 3 |
| SUNITINIB MALATE | Dr. Reddy's | 2021 | 3 |
| INLYTA | PF PRISM CV | 2012 | 3 |
| SORAFENIB TOSYLATE | YABAO PHARM | 2020 | 3 |
| OFEV | Boehringer Ingelheim | 2014 | 3 |
| NEXAVAR | Bayer | 2005 | 3 |
| VOTRIENT | Novartis | 2009 | 2 |
| PAZOPANIB HYDROCHLORIDE | EUGIA PHARMA | 2023 | 2 |
| FOTIVDA | AVEO PHARMS | 2021 | 1 |
| FRUZAQLA | Takeda | 2023 | 1 |
| COMETRIQ | EXELIXIS | 2012 | 1 |
| RESNIBEN | AZURITY | - | - |
VEGFR-3 Drug Modality Landscape
Modalities
Routes of Administration
VEGFR-3 is amenable to small molecule drugs, with oral options available for convenient dosing.
The absence of other modalities represents a whitespace opportunity for novel therapeutic approaches.
VEGFR-3 Clinical Trials 1,788 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on VEGFR-3. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 550 | 349 | 93 | 106 | 79% |
| Phase 2 | 987 | 439 | 202 | 339 | 68% |
| Phase 3 | 212 | 102 | 28 | 82 | 78% |
| Phase 4 | 39 | 24 | 4 | 11 | 86% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved VEGFR-3 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting VEGFR-3. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
VEGFR-3 Drug Approval Timeline (2005 - 2023)
The first VEGFR-3 drug was approved in 2005 (NEXAVAR), and the most recent in 2023 (FRUZAQLA).
The continued approval of new drugs suggests sustained interest and potential for further development.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 14 companies competing
- • Market share by company
Full Drug Portfolio
- • All 16 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 16-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 577 (139 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 VEGFR-3. A trial counts if an approved drug acting on VEGFR-3 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.