PSMA Inhibitors
6 drugsAbout PSMA
Prostate-Specific Membrane Antigen (PSMA), encoded by the FOLH1 gene, is a protein overexpressed in prostate cancer cells. It is a valuable target for imaging and therapy due to its role in tumor progression.
Human genetic studies provide moderate support for PSMA as a therapeutic target, with variants linked to epiretinal membrane (score 0.67), retinopathy (score 0.65), and type 2 diabetes (score 0.60). Strong eQTL/pQTL signals further support its role in disease.
PSMA is targeted by 6 FDA-approved drugs, including PYLARIFY, GOZELLIX, LOCAMETZ, POSLUMA, and GALLIUM GA 68 GOZETOTIDE. These drugs are split between small molecule and peptide modalities, with applications primarily in oncology.
PSMA Genetic Evidence Moderate
Genetic evidence offers moderate support for PSMA, with a max score of 0.67 linking it to epiretinal membrane.
Further investigation into the genetic links could reveal novel therapeutic opportunities beyond oncology.
Evidence Across Diseases
20 totalGWAS and other genetic studies link FOLH1 to 30 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for FOLH1 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 PSMA Drugs
Five companies have approved PSMA-targeting drugs, including PROGENICS PHARMS INC, TELIX INNOVATIONS and Novartis.
The relatively unconcentrated market suggests opportunities for new entrants with differentiated PSMA-targeted therapies.
PSMA Drug Modality Landscape
Modalities
Routes of Administration
PSMA is primarily targeted by peptide modalities (50% of approved drugs).
Exploring alternative modalities like antibodies or PROTACs could provide a competitive advantage.
📈 Modality Evolution
Peptides pioneered PSMA targeting (2020), with small molecules entering more recently (2021).
PSMA Clinical Trials 22 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on PSMA. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 7 | 1 | 2 | 4 | 33% |
| Phase 2 | 9 | 3 | 0 | 6 | 100% |
| Phase 3 | 2 | 1 | 0 | 1 | 100% |
| Phase 4 | 4 | 0 | 1 | 3 | 0% |
Top Sponsors
By Modality
Top Conditions
PSMA Drug Approval Timeline (2020 - 2025)
Metastatic Castration-Resistant Prostate Cancer
The first PSMA-targeting drug was approved in 2020, with the most recent approval in 2025, spanning 6 years.
The recent approval of GOZELLIX suggests continued interest and potential for further development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 6 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 6-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 17 (4 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 PSMA. A trial counts if an approved drug acting on PSMA 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.