IDH1 Inhibitors
3 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.
IDH1 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 IDH1 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.
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.
IDH1 Clinical Trials 75 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on IDH1. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 33 | 9 | 6 | 18 | 60% |
| Phase 2 | 31 | 2 | 1 | 28 | 67% |
| Phase 3 | 10 | 0 | 0 | 10 | - |
| Phase 4 | 1 | 0 | 0 | 1 | - |
Top Sponsors
By Modality
Top Conditions
IDH1 Drug Approval Timeline (2018 - 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.
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Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 3 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 3-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 42 (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 IDH1. A trial counts if an approved drug acting on IDH1 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.