Table 3 —
Pharmacologic agents targeting the complement cascade
| Drug | Pharmacological effects | Clinical indication | References | Stage of development |
|---|---|---|---|---|
| ALXN-5500 | Antibody against C5 | Immunological disorders | Alexion Pharmaceuticals, Inc. website | Phase 1 trials |
| AMY-101 (Cp40) | Inhibits C3 cleavage | Gingivitis C3 glomerulopathy | NCT03694444 PMID: 25982307 | Phase 2 trials |
| AMY-201 | Factor H analog | PNH | PMID: 23616575 | Phase 1 trials |
| APL-1 | Inhibits C3 cleavage | Periodontitis | PMID: 27021500 | Phase 2 trials |
| APL-2 | Inhibits C3 cleavage | Age-related macular degeneration PNH | NCT02503332 | Phase 2 trials |
| ARC-1905 | Anti-C5 aptamer | Age-related macular degeneration | NCT00950638 | Phase 1 trials |
| Avacopan (CCX-168) | C5aR1 antagonist | ANCA vasculitis C3 glomerulopathy Hidradenitis suppurativa | NCT02994927 NCT03301467 NCT03852472 | Phase 3 trials |
| Bikaciomab | Antibody against factor Bb | Age-related macular degeneration | Patent US8981060 | Phase 1 trials |
| C6-antisense oligonucleotide | Decreased expression of C6 | Traumatic brain injury | PMID: 24489093 | Preclinical |
| C6-specific antibody | Inhibits C6 | Traumatic brain injury | PMID: 26493766 | Preclinical |
| Cemdisiran (ALN-CC5) | siRNA directed against C5 | IgA nephropathy Thrombotic microangiopathy | NCT03841448 NCT02352493 | Phase 2 trials |
| CLG561 | Antibody against properdin | Age-related macular degeneration | NCT02515942 | Phase 2 trials |
| Compstatin | Inhibits C3 cleavage | Age-related macular degeneration | PMID: 25678219 | Phase 2 trials |
| Coversin (rVA576) | Inhibits C5 cleavage and inactivates LTB4 | PNH HUS Atopic keratoconjunctivitis | NCT03829449 NCT04037891 | Phase 2 and 3 trials |
| Danicopan (ACH-4471) | Factor D inhibitor | C3 glomerulopathy | NCT03459443 | Phase 2 trials |
| DF2593A | C5aR1 antagonist | Chronic pain syndromes | PMID: 25385614 | Phase 1 trials |
| DF2593A | C5aR1 antagonist | Chronic pain syndromes | PMID: 25385614 | Phase 1 trials |
| DF2593A | C5aR1 antagonist | Chronic pain syndromes | PMID: 25385614 | Phase 1 trials |
| Eculizumab | Antibody against C5 | PNH Atypical HUS MG NMO | NCT00867932 NCT02205541 NCT02301624 NCT01892345 | Approved (Soliris®) |
| IFX-1 | Antibody against C5a | Sepsis Hidradenitis suppurativa ANCA vasculitis | NCT02246595 NCT03001622 NCT03712345 | Phase 2 trials |
| Lampalizumab (FCFD4514S) | Antibody against factor D | Age-related macular degeneration | NCT02288559 | Phase 2 trials |
| LFG-316 | Antibody against C5 | PNH Age-related macular degeneration Thrombotic microangiopathy | NCT02534909 NCT01527500 NCT02763644 | Phase 2 trials |
| LNP023 | Factor B inhibitor | C3 glomerulopathy PNH | NCT03439839 NCT03896152 | Phase 2 trials |
| Mirococept (APT-070) | CR1 analog (inhibitor) | Protection against ischemia-reperfusion injury | PMID: 28587616 | Phase 1 trials |
| Narsoplimab (OMS-721) | Antibody against MASP-2 | Thrombotic microangiopathy IgA nephropathy | NCT03205995 NCT03608033 | Phase 3 trials |
| NDT-9513727 | C5aR1 inverse agonsit | Inflammatory diseases | PMID: 18753409 | Preclinical |
| NM-9401 | Antibody against properdin | PNH | Patent US8664362B2 | Phase 1 trial |
| NOX-D19 | Anti-C5a aptamer | Asthma | PMID: 23530212 | Preclinical |
| NOX-D20 | Anti-C5a aptamer | Sepsis | PMID: 23887360 | Preclinical |
| Olendalizumab (ALXN1007) | Antibody against C5a | Antiphospholipid antibody syndrome | NCT02128269 | Phase 2 trials |
| PMX-53 | C5aR1 antagonist | Inflammatory diseases | PMID: 21441599 | Preclinical |
| Ravulizumab (ALXN-1210) | Antibody against C5 | PNH, MG, atypical HUS | NCT03406507 NCT03920293 | Phase 3 trials |
| Recombinant human C1 inhibitor | C1 esterase inhibitor | Hereditary angioedema | NCT01108848 | Approved (Berinert®, Cinryze® and Ruconset®) |
| SOBI-002 | Inhibits C5 | Immunological disorders | NCT02083666 | Phase 1 trials |
| Sutimlimab (BIVV009) | Antibody against C1s | Cold agglutinin disease | NCT03347396 | Phase 3 trials |
| TNT-003 | Antibody against C1s | Warm AIHA, cold agglutinin disease | PMID: 25904443 | Preclinical |
| TNT-009 | Antibody against C1s | Warm AIHA, cold agglutinin disease | PMID: 27716293 | Phase 1 trials |
| TP10 (CDX-1135) | Soluble CR1 | Glomerulonephritis | NCT01791686 | Phase 1 trials |
| TT30 (ALXN-1102) | Fusion protein of factor H and CR2 | PNH | NCT01335165 | Phase 1 trials |
AIHA = Autoimmune hemolytic anemia; ANCA = antineutrophil cytoplasmic antibody; C5aR1 = C5a complement receptor 1; CR1 = complement receptor 1; CR2 = complement receptor 2; HUS = hemolytic uremic syndrome; LTB4 = leukotriene B4; MASP = mannose-binding lectin–associated serine protease; MG = myasthenia gravis; NCT = ClinicalTrials.gov number; NMO = neuromyelitis optica; PMID = PubMed identifier; PNH = paroxysmal nocturnal hemoglobinuria; siRNA = small interfering ribonucleic acid.