PDCD1 Inhibitors
11 drugsAbout PDCD1
PDCD1 (programmed cell death protein 1), also known as PD-1 or CD279, is an immune checkpoint protein that regulates T cell activity and prevents excessive immune responses. Cancer cells often exploit this mechanism to evade immune detection. As a result, PDCD1 has become a significant focus in oncology drug development.
Human genetics provide moderate support for PDCD1 as a therapeutic target, with a max genetic score of 0.58 linking it to atopic eczema, allergic rhinitis and asthma. Loss-of-function variants are associated with increased risk of atopic eczema, suggesting activation of PDCD1 may be beneficial.
PDCD1 is targeted by 11 FDA-approved drugs, including KEYTRUDA, OPDIVO, and LIBTAYO, primarily in oncology. These drugs are biologics (other, 6 drugs) or antibodies (5 drugs). Eight companies have approved PDCD1-targeting drugs, including Merck and Bristol-Myers Squibb.
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 80% attractiveness score.
- Emerging modalities (Small molecule) signal innovation opportunity.
- phase1 represents biological uncertainty with 59% completion.
Human Genetic Evidence Moderate
Genetic evidence provides moderate support for PDCD1, with a max score of 0.58 for atopic eczema.
Further research into PDCD1 activation may reveal novel therapies for allergic and immune-related diseases.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in integumentary system disease, immune system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
5 totalGWAS and other genetic studies link PDCD1 to 5 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PDCD1 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 PDCD1-targeting drugs, with Merck and Bristol-Myers Squibb leading the market.
The presence of established players suggests high barriers to entry, requiring strong differentiation.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TEVIMBRA | BEIGENE | 2024 | 4 |
| OPDIVO QVANTIG | Bristol-Myers Squibb | 2024 | 3 |
| KEYTRUDA QLEX | Merck | 2025 | 2 |
| ZYNYZ | INCYTE CORP | 2023 | 2 |
| JEMPERLI | GSK | 2021 | 2 |
| OPDUALAG | Bristol-Myers Squibb | 2022 | 2 |
| LOQTORZI | COHERUS BIOSCIENCES INC | 2023 | 1 |
| PENPULIMAB-KCQX | AKESO BIOPHARMA | 2025 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
PDCD1 requires biologic approaches (biologic (other)), likely due to its structure or location.
Consider novel modalities to differentiate from existing antibody and biologic-based therapies.
📈 Modality Evolution
Antibodies pioneered PDCD1 targeting (2014), with other biologics entering more recently (2018).
Clinical Trials 4,555 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 1660 | 560 | 369 | 716 | 60% |
| Phase 2 | 2315 | 608 | 361 | 1328 | 63% |
| Phase 3 | 541 | 161 | 43 | 337 | 79% |
| Phase 4 | 39 | 15 | 3 | 21 | 83% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved PDCD1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting PDCD1. 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 (2014 - 2025)
The first PDCD1-targeting drug was approved in 2014 (KEYTRUDA), with the most recent in 2025 (PENPULIMAB-KCQX).
The continued approval of new drugs indicates ongoing interest and potential for further innovation in this space.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 8 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)
- • 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 4412 clinical trials targeting PDCD1.
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