H1-receptor Inhibitors
4 drugsAbout H1-receptor
The histamine H1 receptor (HRH1) is a G protein-coupled receptor that mediates histamine's effects, influencing inflammation, itching, and smooth muscle contraction. Its activation triggers downstream signaling cascades involved in allergic reactions and neurotransmission.
Human genetics provide moderate support for HRH1 as a therapeutic target, with variants linked to cholelithiasis (score 0.46) and male infertility (score 0.45). Colocalization analysis reveals 20 strong eQTL/pQTL signals, suggesting a role in gene regulation.
HRH1 is targeted by 13 FDA-approved small molecule drugs, including DOXEPIN HYDROCHLORIDE (first approved in 1972) and TONMYA (approved in 2025). Top drugs include KARBINAL ER and HYDROCODONE POLISTIREX AND CHLORPHENIRAMINE POLISTIREX.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Multiple Sclerosis with only 1 trials.
Human Genetic Evidence Moderate
Genetic evidence offers moderate support for HRH1's role in diseases like cholelithiasis and male infertility.
Further research into the causal genes within the 20 strong eQTL/pQTL signals could reveal novel therapeutic opportunities.
Evidence Across Diseases
8 totalGWAS and other genetic studies link HRH1 to 8 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 0.98eQTL/pQTL signals for HRH1 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
Thirteen companies have approved drugs targeting HRH1, including BIONPHARMA and Teva.
The presence of multiple players suggests a competitive market, requiring differentiated strategies for new entrants.
Drug Modality Landscape
Modalities
Routes of Administration
H1-receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide a competitive advantage in targeting HRH1.
Clinical Trials 143 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 29 | 23 | 2 | 4 | 92% |
| Phase 2 | 32 | 25 | 3 | 3 | 89% |
| Phase 3 | 39 | 27 | 3 | 8 | 90% |
| Phase 4 | 43 | 35 | 4 | 4 | 90% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (2009 - 2019)
Drug approvals for HRH1 span 54 years, from 1972 to 2025, indicating sustained interest.
The recent approval of TONMYA suggests continued innovation, but market saturation may necessitate novel approaches.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-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 72 clinical trials targeting H1-receptor.
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