IDH1 Inhibitors
2 drugsAbout IDH1
Isocitrate Dehydrogenase 1 (IDH1) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, a key intermediate in the citric acid cycle, playing a crucial role in cellular metabolism.
Human genetics provide strong validation for IDH1 as a therapeutic target (max score 0.79), with loss-of-function variants protecting against acute myeloid leukemia. Genetic associations include enchondromatosis (score 0.79) and glioma susceptibility (score 0.64), supporting inhibition-based therapies.
IDH1 is targeted by two FDA-approved small molecule drugs: REZLIDHIA (Rigel) and VORANIGO (Servier), with applications in oncology and other therapeutic areas. These approvals highlight the feasibility of modulating IDH1 activity for therapeutic benefit.
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 84% attractiveness score.
- White space opportunity in Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm with only 1 trials.
- phase2 represents biological uncertainty with 0% completion.
Human Genetic Evidence Strong
IDH1 has strong genetic support with a maximum score of 0.79 across six diseases.
Strong genetic support suggests a higher probability of clinical success for IDH1-targeting drugs.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 1 traits
- • Strong signal in hematologic disease, immune system disease, cancer or benign tumor pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
6 totalGWAS and other genetic studies link IDH1 to 6 diseases.
🔗 Colocalization Evidence 1 strong
max H4: 0.84eQTL/pQTL signals for IDH1 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 Drugs
The competitive landscape consists of two companies, Rigel and Servier, with approved IDH1-targeting drugs.
Low market concentration suggests relatively low barriers to entry for new companies targeting IDH1.
Drug Modality Landscape
Modalities
Routes of Administration
IDH1 is amenable to small molecule drugs, with oral options available for convenient dosing.
The exclusive use of small molecules suggests a whitespace opportunity for alternative modalities like antibodies or PROTACs.
Clinical Trials 42 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 21 | 11 | 0 | 10 | 100% |
| Phase 2 | 12 | 1 | 0 | 11 | 100% |
| Phase 3 | 6 | 2 | 0 | 4 | 100% |
| Phase 4 | 3 | 1 | 1 | 1 | 50% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved IDH1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting IDH1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Drug Approval Timeline (2022 - 2024)
The first IDH1-targeting drug was approved in 2022, with the most recent approval in 2024, spanning a 3-year period.
Recent approvals indicate a positive trajectory for IDH1-targeted therapies, but saturation may occur if the pace continues.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 2 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 2-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 34 clinical trials targeting IDH1.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities