Phospholipase A2 Inhibitors
10 drugsAbout Phospholipase A2
Phospholipase A2 (PLA2) enzymes catalyze the hydrolysis of phospholipids, producing fatty acids and lysophospholipids, which act as signaling molecules. These enzymes are involved in various cellular processes, including inflammation and lipid metabolism.
PLA2G2A has moderate genetic support (max score 0.55), with variants linked to familial colorectal cancer, entropion, and ectropion. Loss-of-function variants are associated with increased risk of familial colorectal cancer, suggesting activation may be beneficial.
PLA2 is targeted by 10 FDA-approved small molecule drugs, including LOTEPREDNOL ETABONATE AND TOBRAMYCIN, ZYLET, CLOBEX, DIFLUPREDNATE, and DUREZOL. These drugs are used across pain, immunology, metabolic disorders, and other therapeutic areas.
Phospholipase A2 Genetic Evidence Moderate
PLA2G2A has moderate genetic support with a max score of 0.55.
Further investigation of PLA2 activators may be warranted given the genetic evidence suggesting benefit in familial colorectal cancer.
💡 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, gastrointestinal disease, cancer or benign tumor pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
6 totalGWAS and other genetic studies link PLA2G2A to 6 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PLA2G2A 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 Phospholipase A2 Drugs
Eight companies have approved PLA2-targeting drugs, with Cipla, GALDERMA LABS, and ALIMERA SCIENCES INC among the top players.
The presence of multiple companies indicates a competitive market, requiring a differentiated strategy for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| LOTEPREDNOL ETABONATE AND TOBRAMYCIN | ALEMBIC | 2025 | 9 |
| DIFLUPREDNATE | Dr. Reddy's | 2021 | 3 |
| ILUVIEN | ALIMERA SCIENCES INC | 2014 | 2 |
| BYQLOVI | HARROW EYE | 2024 | 2 |
| RETISERT | BAUSCH AND LOMB INC | 2005 | 1 |
| YUTIQ | ALIMERA SCIENCES INC | 2018 | 1 |
| ASMANEX TWISTHALER | Merck | 2005 | 1 |
Phospholipase A2 Drug Modality Landscape
Modalities
Routes of Administration
Phospholipase A2 is druggable by small molecules, though no oral formulations are currently approved.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage.
Phospholipase A2 Clinical Trials 216 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Phospholipase A2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 28 | 24 | 4 | 0 | 86% |
| Phase 2 | 48 | 32 | 8 | 8 | 80% |
| Phase 3 | 72 | 60 | 5 | 7 | 92% |
| Phase 4 | 68 | 53 | 6 | 9 | 90% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phospholipase A2 Drug Approval Timeline (2003 - 2025)
The first PLA2-targeting drug was approved in 2003, and the most recent in 2025, spanning 23 years.
The continued approval of PLA2-targeting drugs suggests sustained interest and potential for further development.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 8 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
- • Sponsors: 137 (57 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 Phospholipase A2. A trial counts if an approved drug acting on Phospholipase A2 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.