C5 Inhibitors
8 drugsAbout C5
C5 is a key protein in the complement system, part of the innate immune system involved in inflammation and host defense. Its activation triggers a cascade leading to inflammation and cell lysis, making it a target for modulating immune responses.
Human genetics provide strong support for C5 as a drug target (max score 0.84), with loss-of-function variants associated with immunodeficiency. Genetic associations also include coronary artery disease, suggesting potential applications beyond immune disorders. Inhibition of C5 is likely beneficial based on genetic evidence.
C5 is targeted by 7 FDA-approved drugs, including SOLIRIS, ULTOMIRIS, and EPYSQLI, primarily biologics (71%) and antibodies (14%). These drugs are developed by companies like ALEXION PHARM, Regeneron and Amgen, targeting various therapeutic areas.
C5 Genetic Evidence Strong
C5 has strong genetic support with a maximum score of 0.84 linking it to immunodeficiency.
Strong genetic support suggests a higher probability of clinical success for C5-targeting drugs.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 50% directional consistency across 2 traits
- • Strong signal in immune system disease, cardiovascular disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
50% alignedEvidence Across Diseases
11 totalGWAS and other genetic studies link C5 to 11 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 16 strong
max H4: 0.99eQTL/pQTL signals for C5 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 C5 Drugs
The C5 drug market involves 6 companies, including ALEXION PHARM, Regeneron, and Amgen.
The presence of multiple players indicates a moderately competitive market with potential entry barriers.
C5 Drug Modality Landscape
Modalities
Routes of Administration
C5 is druggable by both biologics (6) and small molecules (2), indicating broad therapeutic accessibility.
The dominance of biologics suggests a whitespace opportunity for small molecule C5 inhibitors.
📈 Modality Evolution
Antibodies pioneered C5 targeting (2007), with small molecules entering more recently (2023).
C5 Clinical Trials 155 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on C5. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 23 | 16 | 4 | 3 | 80% |
| Phase 2 | 54 | 33 | 15 | 6 | 69% |
| Phase 3 | 69 | 38 | 8 | 23 | 83% |
| Phase 4 | 9 | 3 | 0 | 6 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
4 Phase 3 trials testing approved C5 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting C5. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
C5 Drug Approval Timeline (2007 - 2024)
The first C5-targeting drug, SOLIRIS, was approved in 2007, with the most recent, PIASKY, approved in 2024.
The 18-year span indicates a mature but still evolving market with continued innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 7 companies competing
- • Market share by company
Full Drug Portfolio
- • All 8 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 8-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 55 (25 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 C5. A trial counts if an approved drug acting on C5 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.