Belimumab Overview

Introduction of Belimumab

Belimumab is a monoclonal antibody targeting BLyS (B-lymphocyte stimulator), a B-cell survival factor. BLyS is also known as B-cell activating factor (BAFF) and is known to induce B-cell proliferation, differentiation and immunoglobulin secretion. In October 2000, Human Genome Sciences (HGS) and Cambridge Antibody Technology (CAT) agreed to co-develop monoclonal antibodies targeted at BLyS. In August 2006, HGS and GlaxoSmithKline (GSK) entered into a co-development and commercialization agreement under which HGS would conduct Phase III trials for belimumab with assistance from GSK. Data from murine models of lupus and patients supports the role of BLyS as a therapeutic target in systemic lupus erythematosus (SLE). Belimumab was not effective in Phase II clinical trials for rheumatoid arthritis. It was moderately effective in Phase II trials for Sjögren syndrome. Under the trade name Benlysta, belimumab received FDA approval for the treatment of SLE on March 9, 2011, despite concerns among advisory committee members that the improvement of 4 points on the SELENA-SLEDA scale was marginal, and despite reservations about additional deaths in the treatment group. It was subsequently approved in Canada and Europe as well.

Mechanism of Action of Belimumab

Systemic lupus erythematosus (SLE) is considered the prototypic autoimmune disease, with aberrations throughout the immune system resulting in diverse clinical manifestations. B cells are central in the pathogenesis of SLE, because they are precursors for plasma cells that secrete antibodies; they also present antigens to T cells and other B cells, and they secrete proinflammatory cytokines. B cells are activated by T cells. B cells and plasmacytoid dendritic cells can also be activated through endosomal toll-like receptors, some of which recognize DNA- and RNA-containing proteins. In patients with SLE, numbers of circulating plasma cells, plasma blasts, and late transitional B cells (a late stage of maturation in B cells) are increased. Higher-than-normal proportions of B cells and T cells are activated, and activation pathways are abnormal, favoring autoimmunity and inflammation. Regulatory cells of several types that suppress B cells and helper T cells are low in numbers or dysfunctional in most patients with SLE. Increased B-cell activation is due in part to increased levels of growth factors, including B-lymphocyte stimulator BLyS (also known as BAFF). BAFF is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. BLyS exists in both membrane-bound and soluble forms and is expressed by monocytes, macrophages and dendritic cells. BLyS can bind to 3 receptors, all of which are expressed by B lymphocytes, namely TACI (TNF transmembrane activator and calcium modulator and cyclophilin ligand interactor), BCMA (B lymphocyte maturation antigen) and BR3 (BAFF/BLyS receptor 3). A further TNF family member, APRIL, can also bind TACI and BCMA with biologic functions similar to BLyS. BAFF is required for B-cell survival, maturation, and activation; germinal-center formation; the development of B cells into plasma cells; and immunoglobulin production. Many of the subsets of maturing B cells are completely dependent on the binding of BAFF receptors by BLyS to survive and mature. Mature, activated B cells differentiate into plasma blasts or memory B cells; memory cells lack BAFF receptors. Belimumab binds to BAFF and reduces the number of circulating B cells. It is possible that belimumab binds primarily to circulating soluble BAFF and therefore does not induce the antibody-dependent cellular cytotoxicity (ADCC) that could be expected from this IgG1-type antibody.

Fig.1 Mechanism of action of Belimumab

Table 1. Clinical Projects of Belimumab*

Table 2. Approved Drugs of Belimumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Powder for injection	120/400 mg	Intravenous infusion	Human Genome Sciences Inc.	March 09, 2011
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Solution	200 mg / mL	Subcutaneous injection	Human Genome Sciences Inc.	March 09, 2011
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Powder for injection	120/400 mg	Intravenous infusion	GlaxoSmithKline LLC	June 20, 2011
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Solution	200 mg / mL	Subcutaneous injection	GlaxoSmithKline LLC	June 20, 2011
Benlysta	Lupus Erythematosus, Systemic	Solution	200 mg / mL	Subcutaneous injection	Glaxo Group Ltd.	June 13, 2011
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Powder for injection	120/400 mg	Intravenous infusion	GlaxoSmithKline Inc.	August 24, 2011
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Solution	200 mg / mL	Subcutaneous injection	GlaxoSmithKline Inc.	December 7, 2017
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Powder for injection	120/400 mg	Intravenous infusion	GlaxoSmithKline Australia Pty Ltd	October 18, 2012
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Solution	200 mg / mL	Subcutaneous injection	GlaxoSmithKline K.K.	September 27, 2017
Benlysta	Active, Autoantibody-Positive Systemic Lupus Erythematosus (SLE)	Powder for injection	120/400 mg	Intravenous infusion	GlaxoSmithKline K.K.	September 27, 2017

What We Provide

Therapeutic Antibody

Belimumab

We provide high-quality Belimumab 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=Belimumab

** Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125370
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761043
https://www.ema.europa.eu/en/medicines/human/EPAR/benlysta
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=85508
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=85509
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=95945
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=75672
http://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/3999445D1
http://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/3999445G1

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