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Details on Person Activation of the complement system significantly contribute...
| Class:Id | Summation:9691612 |
|---|---|
| _displayName | Activation of the complement system significantly contribute... |
| _timestamp | 2025-07-10 11:01:09 |
| created | [InstanceEdit:9691596] Jassal, Bijay, 2020-06-18 |
| literatureReference | [LiteratureReference:9691613] Complement-targeted therapy: development of C5- and C5a-targeted inhibition [LiteratureReference:9691624] Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv [LiteratureReference:9691608] Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria [LiteratureReference:9691593] Design and preclinical characterization of ALXN1210: A novel anti-C5 antibody with extended duration of action [LiteratureReference:9691687] Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial [LiteratureReference:9956954] C5 inhibitor avacincaptad pegol treatment for geographic atrophy: A comprehensive review [LiteratureReference:9956990] Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody [LiteratureReference:9956959] Crovalimab in the paroxysmal nocturnal hemoglobinuria treatment landscape [LiteratureReference:9957010] Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria [LiteratureReference:9956956] Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5 [LiteratureReference:9957013] Population pharmacokinetic analyses of pozelimab in patients with CD55-deficient protein-losing enteropathy (CHAPLE disease) |
| modified | [InstanceEdit:9691727] Jassal, Bijay, 2020-06-18 [InstanceEdit:9956985] Shamovsky, Veronica, 2025-06-17 [InstanceEdit:9960360] Shamovsky, Veronica, 2025-07-10 |
| text | Activation of the complement system significantly contributes to the pathogenesis of numerous acute and chronic diseases. Monoclonal antibodies (mAbs) that recognize the human complement protein C5 have been shown to effectively block C5 cleavage, thereby preventing the generation of pro-inflammatory complement components (Thomas et al. 1996, review Horiuchi & Tsukamoto 2016). The mAb eculizumab was the first therapeutic for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (Rother et al. 2007). Ravulizumab, also used to treat PNH, was engineered from eculizumab to have an inherently longer circulating half-life so as to extend dosing intervals (Sheridan et al. 2018). Crovalimab is another long-acting anti-C5 monoclonal antibody developed for the treatment of PNH, offering an alternative to both ravulizumab and eculizumab. Unlike these antibodies, crovalimab binds a distinct epitope located on the β-chain of C5 and remains effective in individuals with C5 polymorphisms. Crovalimab is designed to dissociate from C5 in acidic endosomes in a pH-dependent manner, allowing the antibody to be recycled and sustain complement inhibition. Additionally, crovalimab employs isoelectric point engineering to enhance uptake and clearance of C5 at lower doses (Sampei et al. 2018; Cosson et al. 2025; reviewed by Röth et al. 2024). Tesidolumab is an investigational mAb targeting complement C5, inhibiting terminal complement activation. Zilucoplan is a small macrocyclic peptide that binds to C5 with high affinity and specificity. It is being investigated for the treatment of myasthenia gravis (MG), a rare autoimmune disease (Howard et al. 2020). Pozelimab is a monoclonal antibody designed to block the activity of C5 in patients with CHAPLE disease, a rare genetic disorder caused by CD55 deficiency and characterized by excessive complement activation, angiopathic thrombosis, and protein-losing enteropathy (Latuszek et al. 2020; Lin et al., 2024). Additionally, avacincaptad pegol, a pegylated RNA aptamer, selectively binds complement component C5, preventing its cleavage into C5a and C5b. By inhibiting C5 activation, it may help treat geographic atrophy (GA) secondary to age-related macular degeneration (AMD) (reviewed by Danzig et al. 2024). |
| (summation) | [Reaction:9691621] C5 binds C5 inhibitors [Homo sapiens] |
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