vilobelimab

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Ligands
vilobelimab

GtoPdb Ligand ID: 11346

Synonyms: CaCP-29 | Gohibic® | IFX-1

vilobelimab is an approved drug

Comment: Vilobelimab (IFX-1) is a chimeric IgG4 monoclonal antibody against the terminal complement component, anaphylatoxin C5a. It was developed for potential to treat complement mediated inflammatory diseases. Vilobelimab blocks C5a/C5aR1 signalling in subsets of myeloid-derived suppressor cells (MDSCs) and neutrophils.

References
1. Bekker P, Dairaghi D, Seitz L, Leleti M, Wang Y, Ertl L, Baumgart T, Shugarts S, Lohr L, Dang T et al.. (2016) Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study. PLoS ONE, 11 (10): e0164646. [PMID:27768695]
2. Carvelli J, Demaria O, Vély F, Batista L, Chouaki Benmansour N, Fares J, Carpentier S, Thibult ML, Morel A, Remark R et al.. (2020) Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis. Nature, 588 (7836): 146-150. [PMID:32726800]
3. Giamarellos-Bourboulis EJ, Argyropoulou M, Kanni T, Spyridopoulos T, Otto I, Zenker O, Guo R, Riedemann NC. (2020) Clinical efficacy of complement C5a inhibition by IFX-1 in hidradenitis suppurativa: an open-label single-arm trial in patients not eligible for adalimumab. Br J Dermatol, 183 (1): 176-178. [PMID:31954061]
4. Hawksworth OA, Li XX, Coulthard LG, Wolvetang EJ, Woodruff TM. (2017) New concepts on the therapeutic control of complement anaphylatoxin receptors. Mol Immunol, 89: 36-43. [PMID:28576324]
5. Jayne D. (2019) Complement inhibition in ANCA vasculitis. Nephrol Ther, 15 (6): 409-412. [PMID:31631015]
6. Kanni T, Zenker O, Habel M, Riedemann N, Giamarellos-Bourboulis EJ. (2018) Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?. Br J Dermatol, 179 (2): 413-419. [PMID:29405257]
7. Lee A. (2022) Avacopan: First Approval. Drugs, 82 (1): 79-85. [PMID:34826105]
8. Li XX, Lee JD, Massey NL, Guan C, Robertson AAB, Clark RJ, Woodruff TM. (2020) Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function. Biochem Pharmacol, 180: 114156. [PMID:32682759]
9. Lim EHT, Vlaar APJ, de Bruin S, Rückinger S, Thielert C, Habel M, Guo R, Burnett BP, Dickinson J, Brouwer MC et al.. (2023) Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients. Intensive Care Med Exp, 11 (1): 37. [PMID:37332066]
10. Lu JD, Milakovic M, Ortega-Loayza AG, Marzano AV, Alavi A. (2020) Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1. Expert Opin Investig Drugs, 29 (11): 1179-1185. [PMID:32880206]
11. Monk PN, Scola AM, Madala P, Fairlie DP. (2007) Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol, 152 (4): 429-48. [PMID:17603557]
12. van Amstel RBE, Slim MA, Lim EHT, Rückinger S, Seymour CW, Burnett BP, Bos LDJ, van Vught LA, Riedemann NC, van de Beek D et al.. (2024) Heterogeneity of treatment effect of vilobelimab in COVID-19: a secondary analysis of a randomised controlled trial. Crit Care, 28 (1): 210. [PMID:38943192]
13. Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, Ter Horst L, Bulle EB, van Baarle FEHP, van de Poll MCG et al.. (2020) Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol, 2 (12): e764-e773. DOI: 10.1016/S2665-9913(20)30341-6 [PMID:33015643]

References

1. Bekker P, Dairaghi D, Seitz L, Leleti M, Wang Y, Ertl L, Baumgart T, Shugarts S, Lohr L, Dang T et al.. (2016)
Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.
PLoS ONE, 11 (10): e0164646. [PMID:27768695]

2. Carvelli J, Demaria O, Vély F, Batista L, Chouaki Benmansour N, Fares J, Carpentier S, Thibult ML, Morel A, Remark R et al.. (2020)
Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.
Nature, 588 (7836): 146-150. [PMID:32726800]

3. Giamarellos-Bourboulis EJ, Argyropoulou M, Kanni T, Spyridopoulos T, Otto I, Zenker O, Guo R, Riedemann NC. (2020)
Clinical efficacy of complement C5a inhibition by IFX-1 in hidradenitis suppurativa: an open-label single-arm trial in patients not eligible for adalimumab.
Br J Dermatol, 183 (1): 176-178. [PMID:31954061]

4. Hawksworth OA, Li XX, Coulthard LG, Wolvetang EJ, Woodruff TM. (2017)
New concepts on the therapeutic control of complement anaphylatoxin receptors.
Mol Immunol, 89: 36-43. [PMID:28576324]

5. Jayne D. (2019)
Complement inhibition in ANCA vasculitis.
Nephrol Ther, 15 (6): 409-412. [PMID:31631015]

6. Kanni T, Zenker O, Habel M, Riedemann N, Giamarellos-Bourboulis EJ. (2018)
Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?.
Br J Dermatol, 179 (2): 413-419. [PMID:29405257]

7. Lee A. (2022)
Avacopan: First Approval.
Drugs, 82 (1): 79-85. [PMID:34826105]

8. Li XX, Lee JD, Massey NL, Guan C, Robertson AAB, Clark RJ, Woodruff TM. (2020)
Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function.
Biochem Pharmacol, 180: 114156. [PMID:32682759]

9. Lim EHT, Vlaar APJ, de Bruin S, Rückinger S, Thielert C, Habel M, Guo R, Burnett BP, Dickinson J, Brouwer MC et al.. (2023)
Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients.
Intensive Care Med Exp, 11 (1): 37. [PMID:37332066]

10. Lu JD, Milakovic M, Ortega-Loayza AG, Marzano AV, Alavi A. (2020)
Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1.
Expert Opin Investig Drugs, 29 (11): 1179-1185. [PMID:32880206]

11. Monk PN, Scola AM, Madala P, Fairlie DP. (2007)
Function, structure and therapeutic potential of complement C5a receptors.
Br J Pharmacol, 152 (4): 429-48. [PMID:17603557]

12. van Amstel RBE, Slim MA, Lim EHT, Rückinger S, Seymour CW, Burnett BP, Bos LDJ, van Vught LA, Riedemann NC, van de Beek D et al.. (2024)
Heterogeneity of treatment effect of vilobelimab in COVID-19: a secondary analysis of a randomised controlled trial.
Crit Care, 28 (1): 210. [PMID:38943192]

13. Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, Ter Horst L, Bulle EB, van Baarle FEHP, van de Poll MCG et al.. (2020)
Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial.
Lancet Rheumatol, 2 (12): e764-e773. DOI: 10.1016/S2665-9913(20)30341-6 [PMID:33015643]