Lirentelimab

Lirentelimab (sold under the brand name AK002) is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis.[2] Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.[3]

Lirentelimab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetSIGLEC8
Clinical data
Trade namesAK002
Routes of
administration		Intravenous
Identifiers
CAS Number
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6408H9884N1700O2006S46
Molar mass144308.221 g·mol−1

Mechanism of action

In individuals with asthma, Siglec-8 expression is increased on the surface of eosinophils and mast cells in sputum.[4] Lirentelimab depletes eosinophils via antibody-dependent natural killer cell mediated cytotoxicity.

Pharmacology

Lirentelimab is a humanized, nonfucosylated IgG1 monoclonal antibody that targets Siglec-8.[5] Siglec-8 is an inhibitory receptor present on eosinophils and mast cells, with low level expression on basophils.[2][6] Interleukin-5, granulocyte-macrophage colony stimulating factor, and interleukin-33 enhance anti-Siglec-8 mediated destruction of eosinophils.[6] Lirentelimab inhibits mast cells' IgE-mediated degranulation and de novo synthesis of prostaglandin D2 in vitro.[6]

Adverse events

Mild-to-moderate infusion reactions may occur with lirentelimab, which tend to occur following the first infusion only.[3]

Research

Lirentelimab has been studied for the treatment of chronic spontaneous urticaria, indolent systemic mastocytosis, and severe allergic conjunctivitis.[5]

References
  1. "Lirentelimab". KEGG Drug Database.
  2. Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, et al. (October 2020). "Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis". The New England Journal of Medicine. 383 (17): 1624–1634. doi:10.1056/NEJMoa2012047. PMC 7600443. PMID 33085861.
  3. Young A (October 29, 2019). "Therapeutic antibody effective in eosinophilic gastritis". Healio. Retrieved 14 December 2020.
  4. Kerr SC, Gonzalez JR, Schanin J, Peters MC, Lambrecht BN, Brock EC, et al. (August 2020). "An anti-siglec-8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells". Clinical and Experimental Allergy. 50 (8): 904–914. doi:10.1111/cea.13681. PMID 32542913. S2CID 219702648.
  5. Johal KJ, Saini SS (October 2020). "Current and emerging treatments for chronic spontaneous urticaria". Annals of Allergy, Asthma & Immunology. 125 (4): 380–387. doi:10.1016/j.anai.2019.08.465. PMC 7056515. PMID 31494233.
  6. Youngblood BA, Brock EC, Leung J, Falahati R, Bryce PJ, Bright J, et al. (2019). "AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice". International Archives of Allergy and Immunology. 180 (2): 91–102. doi:10.1159/000501637. PMID 31401630.
  • "Lirentelimab". Drug Information Portal. U.S. National Library of Medicine.
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