GnRH receptor Inhibitors
12 drugsAbout GnRH receptor
The Gonadotropin-Releasing Hormone receptor (GnRH receptor) regulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the pituitary gland, impacting reproductive function. As a clinically validated target, it plays a key role in various physiological processes.
Human genetics strongly supports GNRHR as a therapeutic target (max score 0.93), with variants linked to hypogonadotropic hypogonadism (score 0.93) and hypopituitarism (score 0.70). Loss-of-function variants increase disease risk, suggesting activation may be beneficial.
GnRH receptor is targeted by 12 FDA-approved small molecule drugs, including LUPRON DEPOT and MYFEMBREE, primarily for oncology (8 drugs) and other indications (4 drugs). These drugs have been approved over a 33-year span.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Stage IIC Prostate Cancer AJCC v8 with only 4 trials.
Human Genetic Evidence Strong
GNRHR has strong genetic support with a max score of 0.93, linking it to 11 diseases.
Strong genetic support suggests a higher probability of clinical trial success for GnRH receptor-targeted therapies.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in genetic, familial or congenital disease, endocrine system disease, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
11 totalGWAS and other genetic studies link GNRHR to 11 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 3 strong
max H4: 0.94eQTL/pQTL signals for GNRHR 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
Eight companies have approved GnRH receptor drugs, including INVAGEN PHARMS and AbbVie.
The presence of multiple players indicates a moderately competitive market with potential entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| ELIGARD KIT | TOLMAR | 2002 | 1 |
| SUPPRELIN LA | ENDO OPERATIONS | 2007 | 1 |
| LEUPROLIDE ACETATE FOR DEPOT SUSPENSION | INVAGEN PHARMS | 2018 | 1 |
| TRIPTODUR KIT | AZURITY | 2017 | 1 |
| FENSOLVI KIT | TOLMAR | 2020 | 1 |
| ORGOVYX | SUMITOMO PHARMA AM | 2020 | 1 |
| ORILISSA | AbbVie | 2018 | 1 |
| LUPRON DEPOT-PED KIT | AbbVie | 1993 | 1 |
| FIRMAGON | FERRING | 2008 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
GnRH receptor is primarily targeted by small molecule modalities (92% of approved drugs).
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage.
📈 Modality Evolution
Small molecules pioneered GnRH receptor targeting (1989), with peptides entering more recently (1989).
Clinical Trials 584 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 135 | 100 | 13 | 22 | 88% |
| Phase 2 | 203 | 101 | 39 | 63 | 72% |
| Phase 3 | 130 | 89 | 17 | 24 | 84% |
| Phase 4 | 116 | 73 | 18 | 24 | 80% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved GnRH receptor drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting GnRH receptor. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Drug Approval Timeline (1989 - 2021)
The first drug, LUPRON DEPOT, was approved in 1989, and the most recent, MYFEMBREE, in 2021.
The continued approval of new drugs suggests ongoing innovation and market potential in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 8 companies competing
- • Market share by company
Full Drug Portfolio
- • All 12 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 12-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 4 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 361 clinical trials targeting GnRH 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