IDH2 Inhibitors
2 drugsAbout IDH2
Isocitrate Dehydrogenase 2 (IDH2) is a mitochondrial enzyme catalyzing the conversion of isocitrate to α-ketoglutarate, crucial for cellular metabolism. Mutant IDH2 produces D-2-hydroxyglutarate (D-2HG), disrupting cell differentiation and promoting tumorigenesis.
IDH2 is a validated oncology target, supported by strong genetic evidence (max score 0.89) linking it to glioma, D-2-hydroxyglutaric aciduria, and myeloid leukemia. Activation of IDH2 is likely beneficial based on genetic associations.
Two FDA-approved small molecule drugs, IDHIFA and VORANIGO, target IDH2 in oncology and other therapeutic areas. These drugs are marketed by Bristol-Myers Squibb and SERVIER, respectively.
IDH2 Genetic Evidence Strong
IDH2 has strong genetic support (score 0.89) across 10 diseases.
Strong genetic support increases confidence in IDH2-targeting therapies for genetically linked indications.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 50% directional consistency across 2 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease, nutritional or metabolic disease pathways
Cross-Disease Effects
Trade-off: HighDirection of Effect
50% alignedEvidence Across Diseases
10 totalGWAS and other genetic studies link IDH2 to 10 diseases.
Gain-of-function causes disease; inhibition may help
Effect Sizes
Genetic effect on disease risk. OR<1 or β<0 = loss-of-function is protective (inhibiting target may help).
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for IDH2 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 IDH2 Drugs
Bristol-Myers Squibb and SERVIER are the only companies with approved IDH2-targeting drugs.
Limited competition suggests opportunity for new entrants in the IDH2 therapeutic space.
IDH2 Drug Modality Landscape
Modalities
Routes of Administration
IDH2 is amenable to small molecule drugs, with oral options available for convenient dosing.
Explore alternative modalities to differentiate from existing small molecule IDH2 inhibitors.
IDH2 Clinical Trials 48 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on IDH2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 28 | 14 | 4 | 10 | 78% |
| Phase 2 | 16 | 2 | 1 | 12 | 67% |
| Phase 3 | 4 | 0 | 0 | 4 | - |
Top Sponsors
By Modality
Top Conditions
IDH2 Drug Approval Timeline (2017 - 2024)
The first IDH2-targeting drug was approved in 2017, with the most recent in 2024.
Recent approval suggests continued interest and potential in targeting IDH2.
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
- • Sponsors: 27 (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 IDH2. A trial counts if an approved drug acting on IDH2 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.