TPO receptor Inhibitors
4 drugsAbout TPO receptor
The thrombopoietin receptor (TPO receptor), also known as MPL, regulates megakaryocyte development and platelet production, making it a critical target in hematopoiesis. Activation of TPO receptor stimulates cell proliferation and differentiation. It is a key regulator of platelet production.
Human genetic studies provide strong validation for TPO receptor as a therapeutic target (max score 0.92). Loss-of-function variants are associated with essential thrombocythemia (score 0.92), congenital amegakaryocytic thrombocytopenia 1 (score 0.91), and thrombocythemia 2 (score 0.90), suggesting activation is likely beneficial.
TPO receptor is targeted by four FDA-approved drugs: MULPLETA, DOPTELET, DOPTELET SPRINKLE, and NPLATE. These drugs include small molecules (3) and biologics (1), addressing various therapeutic needs in the 'other' therapeutic area.
TPO receptor Genetic Evidence Strong
TPO receptor has strong genetic support with a max score of 0.92 across 13 diseases.
Strong genetic support suggests that clinical trials targeting TPO receptor 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 3 traits
- • Strong signal in hematologic disease, immune system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
13 totalGWAS and other genetic studies link MPL to 13 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 0.97eQTL/pQTL signals for MPL 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 TPO receptor Drugs
Three companies, VANCOCIN ITALIA, AKARX INC, and Amgen, have approved drugs targeting TPO receptor.
The concentrated market indicates high barriers to entry for new companies developing TPO receptor-targeting drugs.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| DOPTELET SPRINKLE | AKARX INC | 2025 | 3 |
TPO receptor Drug Modality Landscape
Modalities
Routes of Administration
TPO receptor is druggable by both biologics (1) and small molecules (3), indicating broad therapeutic accessibility.
The dominance of small molecules suggests a potential whitespace opportunity for novel biologic modalities.
📈 Modality Evolution
other biologics pioneered TPO receptor targeting (2008), with small molecules entering more recently (2018).
TPO receptor Clinical Trials 92 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on TPO receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 8 | 6 | 0 | 2 | 100% |
| Phase 2 | 58 | 16 | 14 | 28 | 53% |
| Phase 3 | 20 | 10 | 2 | 8 | 83% |
| Phase 4 | 6 | 3 | 0 | 3 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved TPO receptor drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting TPO receptor. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
TPO receptor Drug Approval Timeline (2008 - 2025)
The first drug targeting TPO receptor was approved in 2008, with the most recent approval in 2025.
The 18-year span suggests a sustained interest in TPO receptor as a drug target, but potential market saturation.
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: 45 (10 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 TPO receptor. A trial counts if an approved drug acting on TPO 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.