Vasopressin V2 receptor Inhibitors
4 drugsAbout Vasopressin V2 receptor
The Vasopressin V2 receptor (AVPR2) is a GPCR that regulates water reabsorption in the kidneys. Activation of this receptor is critical for maintaining fluid balance in the body.
Human genetic studies provide strong validation for AVPR2 as a therapeutic target (max score 0.87). Loss-of-function variants are linked to nephrogenic diabetes insipidus (score 0.87) and nephrogenic syndrome of inappropriate antidiuresis (score 0.85), suggesting activation may be beneficial.
Four small molecule drugs target AVPR2, including Tolvaptan (Samsca, Jynarque) and Terlivaz. These drugs are approved for cardiovascular and other therapeutic areas.
Vasopressin V2 receptor Genetic Evidence Strong
AVPR2 has strong genetic support with a maximum score of 0.87.
Strong genetic support suggests a higher probability of clinical trial success for AVPR2-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 urinary system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
5 totalGWAS and other genetic studies link AVPR2 to 5 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
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 Vasopressin V2 receptor Drugs
Three companies have approved drugs targeting AVPR2: Apotex, OTSUKA, and MALLINCKRODT IRELAND.
The limited number of players suggests relatively low barriers to entry in the AVPR2 drug market.
Vasopressin V2 receptor Drug Modality Landscape
Modalities
Routes of Administration
Vasopressin V2 receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
The absence of other modalities indicates a whitespace opportunity for novel biologics targeting AVPR2.
Vasopressin V2 receptor Clinical Trials 80 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Vasopressin V2 receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 10 | 10 | 0 | 0 | 100% |
| Phase 2 | 20 | 16 | 3 | 1 | 84% |
| Phase 3 | 28 | 22 | 5 | 1 | 81% |
| Phase 4 | 22 | 17 | 5 | 0 | 77% |
Top Sponsors
By Modality
Vasopressin V2 receptor Drug Approval Timeline (2009 - 2022)
The first drug was approved in 2009 (SAMSCA), and the most recent in 2022 (TERLIVAZ), spanning 14 years.
The recent approval suggests continued interest and potential for further drug development targeting AVPR2.
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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: 41 (11 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 Vasopressin V2 receptor. A trial counts if an approved drug acting on Vasopressin V2 receptor 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.