PDE5 Inhibitors
12 drugsAbout PDE5
Phosphodiesterase 5 (PDE5) is an enzyme that regulates blood flow and smooth muscle relaxation by breaking down cyclic guanosine monophosphate (cGMP). Its activity influences vasodilation and blood pressure. As a result, PDE5 has become a significant drug target.
Human genetic studies provide strong validation for PDE5 (gene symbol PDE5A) as a therapeutic target, with variants linked to coronary artery disease (score 0.72), carotid artery disease (0.51) and obesity (0.47). Loss-of-function variants are protective, suggesting inhibition is likely beneficial.
PDE5 is targeted by 11 FDA-approved small molecule drugs, including Viagra, tadalafil, and vardenafil. These drugs are used to treat cardiovascular conditions and other indications. Multiple companies have approved PDE5 inhibitors, including Aurobindo Pharma, ZYDUS PHARMS, and Viatris.
PDE5 Genetic Evidence Strong
Genetic evidence strongly supports PDE5 as a drug target, with a maximum score of 0.72 for coronary artery disease.
Strong genetic support increases clinical success probability, making PDE5 a promising target for further drug development.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 2 traits
- • Strong signal in cardiovascular disease, nutritional or metabolic disease, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
6 totalGWAS and other genetic studies link PDE5A to 6 diseases.
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PDE5A 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 PDE5 Drugs
Ten companies have approved drugs targeting PDE5, with Aurobindo Pharma, ZYDUS PHARMS, and Viatris as top players.
The competitive landscape is moderately fragmented, suggesting relatively low barriers to entry for new players.
PDE5 Drug Modality Landscape
Modalities
Routes of Administration
PDE5 is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape is saturated with small molecules, suggesting an opportunity for novel modalities like biologics.
PDE5 Clinical Trials 368 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on PDE5. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 108 | 89 | 12 | 7 | 88% |
| Phase 2 | 100 | 58 | 22 | 20 | 73% |
| Phase 3 | 77 | 52 | 14 | 11 | 79% |
| Phase 4 | 83 | 56 | 16 | 10 | 78% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved PDE5 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting PDE5. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
PDE5 Drug Approval Timeline (1998 - 2025)
The first PDE5 inhibitor, Viagra, was approved in 1998, and the most recent, VyBrique, in 2025.
The approval timeline spans 28 years, indicating sustained interest and potential for further innovation in this target space.
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Deep insights for drug target analysis
Competitive Landscape
- • 9 companies competing
- • Market share by company
Full Drug Portfolio
- • All 12 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 12-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 183 (38 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 PDE5. A trial counts if an approved drug acting on PDE5 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.