FXR Inhibitors
3 drugsAbout FXR
The Farnesoid X Receptor (FXR) is a nuclear receptor that regulates bile acid, lipid, and glucose metabolism, playing a key role in metabolic homeostasis. As a ligand-activated transcription factor, FXR modulates the expression of genes involved in these pathways.
Human genetic studies provide strong validation for FXR as a therapeutic target, with variants linked to progressive familial intrahepatic cholestasis (score 0.81). Loss-of-function variants are associated with increased disease risk, suggesting activation may be beneficial.
FXR is targeted by 3 FDA-approved small molecule drugs: CHOLBAM, CHENODIOL, and CTEXLI, developed by MIRUM and LGM PHARMA. These drugs address indications in other therapeutic areas.
FXR Genetic Evidence Strong
Genetic evidence strongly supports FXR's role in diseases like progressive familial intrahepatic cholestasis (score 0.81).
Strong genetic support increases confidence in FXR activation strategies for relevant indications.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in endocrine system disease, nutritional or metabolic disease, gastrointestinal disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
10 totalGWAS and other genetic studies link NR1H4 to 10 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
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 FXR Drugs
MIRUM and LGM PHARMA are the only companies with approved FXR-targeting drugs.
Limited competition suggests an opportunity for new entrants with differentiated FXR modulators.
FXR Drug Modality Landscape
Modalities
Routes of Administration
FXR is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or gene therapies could create differentiation.
FXR Clinical Trials 3 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on FXR. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 1 | 1 | 0 | 0 | 100% |
| Phase 3 | 2 | 2 | 0 | 0 | 100% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
FXR Drug Approval Timeline (2009 - 2025)
The first FXR drug was approved in 2009, with the most recent in 2025, spanning 17 years.
The recent approval suggests renewed interest, but market saturation should be monitored.
Pro Intelligence Preview
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: 2 (1 company)
- • 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 FXR. A trial counts if an approved drug acting on FXR 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.