RARbeta Inhibitors
10 drugsAbout RARbeta
Retinoic acid receptor beta (RARbeta) is a nuclear receptor that regulates cellular differentiation, proliferation, and apoptosis. As a ligand-activated transcription factor, it modulates gene expression by binding to DNA in the presence of retinoids. This mechanism makes RARbeta a drug development target, especially where cellular growth and differentiation are dysregulated.
Human genetics provide strong support for RARbeta as a therapeutic target (max score 0.84), with variants linked to microphthalmia, open-angle glaucoma, and COPD. Activation of RARbeta is likely beneficial based on loss-of-function variants increasing disease risk, suggesting agonist therapies may be effective.
RARbeta is targeted by 4 FDA-approved topical drugs, including RETIN-A, ALTRENO, TWYNEO and ATRALIN, all small molecules. These drugs are approved for other therapeutic areas, highlighting the clinical relevance of modulating RARbeta activity.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARA with only 1 trials.
Human Genetic Evidence Strong
Genetic evidence strongly supports RARB as a drug target, with a maximum score of 0.84 across 45 diseases.
Strong genetic support increases the likelihood of clinical success, suggesting investment in RARbeta-targeting therapies is warranted.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in genetic, familial or congenital disease, disorder of visual system pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link RARB to 45 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 3 strong
max H4: 0.98eQTL/pQTL signals for RARB 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
Three companies, including VALEANT, DOW PHARM, and MAYNE PHARMA, have approved drugs targeting RARbeta.
The market is moderately concentrated, suggesting potential entry barriers for new companies developing RARbeta-targeting drugs.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| FABIOR | MAYNE PHARMA | 2012 | 1 |
| ARAZLO | BAUSCH | 2019 | 1 |
| DUOBRII | BAUSCH | 2019 | 1 |
| ALTRENO | DOW PHARM | 2018 | 1 |
| PANRETIN | ADVANZ PHARMA | 1999 | 1 |
| TWYNEO | MAYNE PHARMA | 2021 | 1 |
| ATRALIN | DOW PHARM | 2007 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
RARbeta is druggable by small molecules, though no oral formulations are currently approved.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage in targeting RARbeta.
Clinical Trials 187 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 53 | 41 | 5 | 7 | 89% |
| Phase 2 | 42 | 25 | 3 | 11 | 89% |
| Phase 3 | 39 | 30 | 3 | 6 | 91% |
| Phase 4 | 53 | 45 | 6 | 2 | 88% |
Top Sponsors
By Modality
Drug Approval Timeline (1971 - 2021)
The first RARbeta-targeting drug was approved in 1971 (RETIN-A), with the most recent approval in 2021 (TWYNEO).
The 51-year span of approvals indicates sustained interest in RARbeta as a target, but also potential market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 companies competing
- • Market share by company
Full Drug Portfolio
- • All 10 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 10-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 85 clinical trials targeting RARbeta.
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