Lebrikizumab Overview

Introduction of Lebrikizumab

Lebrikizumab (INN) is a humanized monoclonal antibody and an experimental immunosuppressive drug for the treatment of asthma that cannot be adequately controlled with inhalable glucocorticoids. The drug was created by Tanox under the name TNX-650, and a phase I clinical trial for refractory Hodgkin’s lymphoma had been performed when Genentech acquired Tanox in 2007. It has successfully completed a Phase II clinical trial for the treatment of asthma.

Mechanism of Action of Lebrikizumab

Asthma is a complex, chronic and heterogeneous inflammatory disease characterised by airway hyper-responsiveness in association with airway inflammation. The cytokine interleukin 13 (IL-13), produced by Th2 cells, a type of white blood cells, is a major effector molecule for T-helper type 2 (Th2) inflammation and is pathogenic in allergic diseases such as asthma. IL-13 is a member of the four-helix bundle short-chain cytokine family, along with the closely related cytokine IL-4, has been shown to drive key disease mechanisms in asthma including airway hyper-responsiveness, mucus hypersecretion, eosinophilia and fibrosis development.

IL-13 mediates its biological effects by binding to two receptors: (1) the heterodimeric combination of IL-13Rα1 and IL-4Rα or (2) IL-13Rα2. Of these, the heterodimeric receptor of IL-13Rα1 and IL-4Rα is also bound by IL-4. IL-13 initially binds to IL-13Rα1 with a modest affinity on one side and then recruiting IL-4Rα on the opposite side with a weak affinity to form a signal transducer and activator of transcription 6 signaling complex in which IL-13 is in the middle of the two receptors, leading to the formation of IL-13/IL-13Rα1/IL-4Rα complexes. In contrast, IL-13 binds to IL-13Rα2 with a very high affinity using the combination of two well separated binding sites, more or less at opposite ends of IL-13 helix D, to interact with all three domains of the IL-13Rα2 extracellular region. IL-13Rα2 lacks a significant cytoplasmic tail and is generally considered to be a decoy involved in removing IL-13 by internalisation. The IL-13Rα1 binding site on IL-13 strongly overlaps with the IL- 13Rα2 binding site, with differences in detail accounting for the large difference in affinity. Differently, the IL-4Rα binding site on IL-13 is distinct from those of IL-13Rα1 and IL-13Rα2, on the opposite side of IL-13 and composed of elements from helices A and C.

Antibodies raised against IL-13 can block its inflammatory effects by interfering with binding to either of the two receptor polypeptides. Lebrikizumab is a monoclonal anti-IL-13 antibody that has shown clinical benefit for the treatment of moderate-to-severe uncontrolled asthma and mproved lung function. Lebrikizumab inhibits IL-13 signaling by binding to IL-13 with very high affinity and blocking IL-13 binding to IL-4Rα. Thereby preventing the formation of an active cytokine/receptor complex consisting of IL-13, IL- 13Rα1, and IL-4Rα, resulting the intrinsic affinity between IL-13 and IL-4Rα alone is too low for direct testing in a similar ELISA assay.

Figure 1 Mechanism of Action of Lebrikizumab

Clinical Projects of Lebrikizumab *

Approved Drugs of Lebrikizumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Lebrikizumab	Asthma	Solution for injection	-	Subcutaneous use	Roche Product Limited	November 27, 2015

What We Provide

Therapeutic Antibody

Lebrikizumab

We provide high-quality Lebrikizumab 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.

Resources
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Lebrikizumab&Search=Apply&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=&rslt=

** Information presented in the table were collected from the following websites:
http://www.ema.europa.eu/docs/en_GB/document_library/PIP_decision/WC500199542.pdf

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