COX-2 Inhibitors
32 drugsAbout COX-2
Cyclooxygenase-2 (COX-2), encoded by the PTGS2 gene, is an enzyme that catalyzes the production of prostaglandins, signaling molecules involved in inflammation and pain.
Human genetics provide moderate support for COX-2 as a therapeutic target (max score 0.65), with loss-of-function variants linked to reduced risk of nephrolithiasis. Inhibition of COX-2 is likely beneficial based on genetic evidence.
COX-2 is targeted by 32 FDA-approved small molecule drugs, including CELEBREX, MELOXICAM, and MEFENAMIC ACID, for immunology, pain, and CNS indications.
COX-2 Genetic Evidence Moderate
Genetic evidence shows moderate support for COX-2 as a target, with a max score of 0.65.
Moderate genetic support suggests further validation studies could increase confidence in clinical trials.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 2 traits
- • Strong signal in urinary system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
2 totalGWAS and other genetic studies link PTGS2 to 2 diseases.
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 0.96eQTL/pQTL signals for PTGS2 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 COX-2 Drugs
The competitive landscape includes 27 companies, with Teva, NOVITIUM PHARMA, and Lupin among the top players.
The fragmented market indicates relatively low barriers to entry, but established players have brand recognition.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| EC-NAPROSYN | ATNAHS PHARMA US | 1994 | 9 |
| CELECOXIB | Apotex | 2014 | 6 |
| ELYXYB | SCILEX PHARMS | 2020 | 6 |
| NAPROXEN AND ESOMEPRAZOLE MAGNESIUM | PHARMOBEDIENT | 2020 | 5 |
| DICLOFENAC SODIUM AND MISOPROSTOL | YUNG SHIN PHARM | 2012 | 4 |
| FLECTOR | IBSA | 2007 | 4 |
| VYSCOXA | CARWIN PHARM ASSOC | 2025 | 4 |
| ARTHROTEC | Pfizer | 1997 | 4 |
| MELOXICAM | AIPING PHARM INC | 2004 | 3 |
| LICART | IBSA INST BIO | 2018 | 3 |
| COXANTO | SOLUBIOMIX | 2023 | 3 |
| DAYPRO | Pfizer | 1992 | 3 |
| FELDENE | Pfizer | 1982 | 2 |
| BROMFENAC SODIUM | RISING | 2011 | 2 |
| CALDOLOR | Apotex | 2009 | 2 |
| OMIDRIA | RAYNER SURGICAL | 2014 | 2 |
| PONSTEL | AVION PHARMS | 1967 | 2 |
| MEFENAMIC ACID | AJENAT PHARMS | 2010 | 2 |
| SUMATRIPTAN AND NAPROXEN SODIUM | Sun Pharma | 2018 | 2 |
| CAMBIA | COSETTE | 2009 | 2 |
| PROLENSA | BAUSCH AND LOMB INC | 2013 | 2 |
| BROMSITE | Sun Pharma | 2016 | 2 |
| SPRIX | COSETTE | 2010 | 1 |
| XIFYRM | AZURITY | 2025 | 1 |
| COMBOGESIC | AFT PHARMS US | 2023 | 1 |
| SYMBRAVO | AXSOME | 2025 | 1 |
| QAMZOVA | NANJING DELOVA | 2025 | 1 |
| ZIPSOR | COSETTE | 2009 | 1 |
| COMBOGESIC IV | Hikma | 2023 | 1 |
COX-2 Drug Modality Landscape
Modalities
Routes of Administration
COX-2 is amenable to small molecule drugs, with oral options available for convenient dosing.
The exclusive use of small molecules suggests an opportunity for novel modalities like antibodies or biologics.
COX-2 Clinical Trials 1,808 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on COX-2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 376 | 298 | 45 | 32 | 87% |
| Phase 2 | 417 | 275 | 70 | 69 | 80% |
| Phase 3 | 376 | 287 | 45 | 41 | 86% |
| Phase 4 | 639 | 428 | 110 | 101 | 80% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved COX-2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting COX-2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
COX-2 Drug Approval Timeline (1967 - 2025)
The first COX-2 inhibitor was approved in 1967 (PONSTEL), with the most recent approval in 2025 (XIFYRM).
The continued approvals over a 59-year span suggest sustained interest and potential for further innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 25 companies competing
- • Market share by company
Full Drug Portfolio
- • All 32 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 32-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 793 (221 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 COX-2. A trial counts if an approved drug acting on COX-2 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.