Ligelizumab Overview

Introduction of Ligelizumab

Ligelizumab (QGE031) is a humanized monoclonal antibody (mAb) designed for the treatment of severe asthma and chronic spontaneous urticaria. his drug was developed by Novartis Pharma AG. As of 2018, ligelizumab is undergoing Phase III trials. It binds with high affinity to the Cε3 domain of IgE. Compared to omalizumab, another US Food and Drug Administration (FDA)-approved mAb targeting IgE, ligelizumab shows six-fold to nine-fold greater suppression of allergen-induced skin prick tests in vivo. The estimated plasma half-life is 20 days with over 95% suppression of allergen-induced skin prick test responses 6 weeks post dose by comparison with 41% for omalizumab. It also provides greater and longer suppression of free IgE and IgE on the surface of circulating basophils as compared to omalizumab. These findings suggest that ligelizumab may be more potent than omalizumab in the treatment of chronic spontaneous urticaria (CSU). There is an ongoing multi-center, randomized, double-blind, placebo, and active-controlled phase 2b dose-finding study of ligelizumab as add-on therapy to investigate the efficacy and safety in patients with CSU (NCT02477332). The effects of ligelizumab and omalizumab as control, in this trial, are assessed by measurements of wheal numbers, itch intensity and the urticaria activity scores at baseline, at week 12 and at week 20. The study includes four different doses of ligelizumab given as subcutaneous injections of omalizumab 300 mg monthly as a positive control and a placebo arm. The estimated enrolment is 360 CSU patients and anticipated study completion date is March 2017.

Mechanism of Action of Ligelizumab

IgE has unique properties among immunoglobulin isotypes and plays a central role in the pathophysiology of acute allergic reactions and chronic inflammatory allergic diseases. In genetically susceptible individuals, exposure to specific allergens results in an increase of specific IgE, which can bind onto effector cells through a high affinity receptor known as FcεRI expressed in mast cells and basophils. IgE is very short-lived in plasma (about 1 day), but receptor-bound IgE can remain fixed to cells in tissues for weeks or months. Moreover, IgE binding to FcεRI increases cell survival and receptor upregulation and upon contact with a specific allergen induces the release of pharmacologically active mediators stored in the granules of mast cells (MC) and blood basophils (BS), resulting in clinical manifestations of type 1 hypersensitivity. In type 1 hypersensitivity, in the initial phase, an antigen (the allergen) is presented to antigen-specific CD4+ Th2 cells, which stimulate B-cell production of IgE antibodies that are also antigen-specific. During sensitization, the IgE antibodies bind to FcεRI on the surface of tissue MC and blood BS. Later exposure to the same allergen cross-links the bound IgE on sensitized cells, resulting in degranulation and secretion of preformed pharmacologically active mediators such as histamine. All of this occurs as an immediate reaction, starting within seconds. A late reaction caused by the induced synthesis and release of leukotrienes, chemokines, and cytokines by the activated mast cells allows the recruitment of other leukocytes, eosinophils, basophils, and Th2 lymphocytes to the site of inflammation. The allergic reaction includes symptoms like cough, bronchospasm, wheezing, diarrhea, and urticaria due to this process. Omalizumab binds the Cε3 domain of free IgE preventing it from binding to FcεRI, further dampening the effector cell response to allergen.

Fig 1. Mechanism of Action of Ligelizumab

Table 1. Clinical Projects of Ligelizumab *

What We Provide

Therapeutic Antibody

Ligelizumab

We provide high-quality Ligelizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Ligelizumab

For research use only. Not intended for any clinical use.