PDE5 Inhibitors
11 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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Head and Neck Cancer with only 2 trials.
Human 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 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.
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.
Clinical Trials 406 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 124 | 101 | 12 | 11 | 89% |
| Phase 2 | 110 | 60 | 24 | 26 | 71% |
| Phase 3 | 92 | 62 | 14 | 16 | 82% |
| Phase 4 | 80 | 55 | 18 | 7 | 75% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
2 Phase 3 trials 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.
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.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 10 companies competing
- • Market share by company
Full Drug Portfolio
- • All 11 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 11-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 205 clinical trials targeting PDE5.
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