CTLA4 Inhibitors
2 drugsAbout CTLA4
Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), also known as CD152, is a receptor on T cells that negatively regulates the immune system. It prevents T cell activation, maintaining immune homeostasis but also potentially hindering anti-cancer responses. This inhibitory function makes CTLA4 a key immunotherapeutic target.
Human genetic studies provide strong validation for CTLA4 as a therapeutic target (max score 0.88). Variants are linked to hypothyroidism (0.88), type 1 diabetes (0.87), and rheumatoid arthritis (0.86). Strong eQTL/pQTL signals further support CTLA4's role in disease.
CTLA4 is targeted by two FDA-approved drugs: YERVOY and IMJUDO. These include one antibody and one biologic (other) modality. YERVOY (Bristol-Myers Squibb) has 9 indications, while IMJUDO (AstraZeneca) has 2, primarily in oncology.
CTLA4 Genetic Evidence Strong
CTLA4 has strong genetic support with a max score of 0.88 linked to multiple autoimmune diseases.
Strong genetic support suggests a higher likelihood of clinical success for CTLA4-targeting therapies.
Evidence Across Diseases
20 totalGWAS and other genetic studies link CTLA4 to 43 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for CTLA4 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 CTLA4 Drugs
Bristol-Myers Squibb and AstraZeneca are the dominant players in the CTLA4 drug market.
High market concentration suggests significant barriers to entry for new companies.
CTLA4 Drug Modality Landscape
Modalities
Routes of Administration
CTLA4 requires biologic approaches (biologic (other)), likely due to its structure or location.
Explore novel modalities beyond antibodies to differentiate from existing CTLA4-targeting therapies.
📈 Modality Evolution
Antibodies pioneered CTLA4 targeting (2011), with other biologics entering more recently (2022).
CTLA4 Clinical Trials 920 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on CTLA4. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 378 | 180 | 92 | 103 | 66% |
| Phase 2 | 455 | 178 | 78 | 196 | 70% |
| Phase 3 | 81 | 41 | 4 | 36 | 91% |
| Phase 4 | 6 | 3 | 1 | 2 | 75% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
6 Phase 3 trials testing approved CTLA4 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting CTLA4. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
CTLA4 Drug Approval Timeline (2011 - 2022)
The first CTLA4-targeting drug was approved in 2011, with the most recent in 2022.
The approval timeline indicates continued interest and potential for further development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 2 companies competing
- • Market share by company
Full Drug Portfolio
- • All 2 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 2-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 312 (84 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 CTLA4. A trial counts if an approved drug acting on CTLA4 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.