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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Fractures, Open with only 2 trials.
Human 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 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 |
|---|---|---|---|
| DIFLUPREDNATE | Viatris | 2021 | 3 |
| DUREZOL | Novartis | 2008 | 3 |
| BYQLOVI | HARROW EYE | 2024 | 2 |
| ILUVIEN | ALIMERA SCIENCES INC | 2014 | 2 |
| ASMANEX TWISTHALER | Merck | 2005 | 1 |
| YUTIQ | ALIMERA SCIENCES INC | 2018 | 1 |
| RETISERT | BAUSCH AND LOMB | 2005 | 1 |
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.
Clinical Trials 251 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 45 | 38 | 5 | 2 | 88% |
| Phase 2 | 57 | 39 | 9 | 9 | 81% |
| Phase 3 | 77 | 63 | 6 | 8 | 91% |
| Phase 4 | 72 | 57 | 7 | 8 | 89% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
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
- • 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 124 clinical trials targeting Phospholipase A2.
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