GnRH receptor Inhibitors
13 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.
GnRH receptor 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 GnRH receptor 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 |
|---|---|---|---|
| TRELSTAR | VERITY | 2000 | 1 |
| LEUPROLIDE ACETATE FOR DEPOT SUSPENSION | INVAGEN PHARMS | 2018 | 1 |
| ORILISSA | AbbVie | 2018 | 1 |
| FENSOLVI KIT | TOLMAR | 2020 | 1 |
| SUPPRELIN LA | ENDO OPERATIONS | 2007 | 1 |
| TRIPTODUR KIT | AZURITY | 2017 | 1 |
| LUPRON DEPOT-PED KIT | AbbVie | 1993 | 1 |
| ELIGARD KIT | TOLMAR | 2002 | 1 |
| FIRMAGON | FERRING | 2008 | 1 |
| ORGOVYX | SUMITOMO PHARMA AM | 2020 | 1 |
GnRH receptor Drug Modality Landscape
Modalities
Routes of Administration
GnRH receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage.
GnRH receptor Clinical Trials 559 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on GnRH receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 111 | 82 | 12 | 16 | 87% |
| Phase 2 | 202 | 97 | 42 | 63 | 70% |
| Phase 3 | 132 | 89 | 18 | 25 | 83% |
| Phase 4 | 114 | 69 | 20 | 25 | 78% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
GnRH receptor 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
- • 9 companies competing
- • Market share by company
Full Drug Portfolio
- • All 13 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 13-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 288 (86 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 GnRH receptor. A trial counts if an approved drug acting on GnRH receptor 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.