IGF-1R Inhibitors
4 drugsAbout IGF-1R
The Insulin-like Growth Factor 1 Receptor (IGF-1R) is a receptor tyrosine kinase crucial for cell growth, differentiation, and survival. It plays a key role in intracellular signaling pathways like MAPK/ERK and PI3K/AKT, influencing cell proliferation and apoptosis.
Human genetic studies provide strong support for IGF1R as a therapeutic target (max score 0.88). Variants are linked to growth delay (score 0.88), genetic disorders (score 0.85), and gout (score 0.80), with loss-of-function variants increasing disease risk.
IGF-1R is targeted by 4 FDA-approved drugs, including INCRELEX, TEPEZZA, ALUNBRIG, and ZYKADIA. These drugs are split between biologics and small molecules, with applications in oncology and other therapeutic areas.
IGF-1R Genetic Evidence Strong
Strong genetic evidence supports IGF1R's role in various diseases, with a maximum score of 0.88.
Strong genetic support increases confidence in target validation and likelihood of clinical success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in genetic, familial or congenital disease, endocrine system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link IGF1R to 44 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 IGF1R 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 IGF-1R Drugs
Four companies have approved drugs targeting IGF-1R, including HORIZON THERAPEUTICS IRELAND and Takeda.
A relatively unconcentrated market suggests opportunities for new entrants with differentiated IGF-1R inhibitors.
IGF-1R Drug Modality Landscape
Modalities
Routes of Administration
IGF-1R is druggable by both biologics (2) and small molecules (1), indicating broad therapeutic accessibility.
Consider exploring novel modalities to differentiate from existing IGF-1R therapies.
📈 Modality Evolution
other biologics pioneered IGF-1R targeting (2005), with small molecules entering more recently (2017).
IGF-1R Clinical Trials 70 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on IGF-1R. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 29 | 16 | 7 | 6 | 70% |
| Phase 2 | 27 | 6 | 15 | 6 | 29% |
| Phase 3 | 9 | 8 | 0 | 1 | 100% |
| Phase 4 | 5 | 3 | 0 | 2 | 100% |
Top Sponsors
By Modality
Top Conditions
IGF-1R Drug Approval Timeline (2005 - 2020)
Approved IGF-1R drugs span from 2005 (INCRELEX) to 2020 (TEPEZZA), a 16-year period.
The recent approval of TEPEZZA suggests continued interest and potential for further drug development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 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: 34 (5 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 IGF-1R. A trial counts if an approved drug acting on IGF-1R 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.