Description

Belimumab was approved by the U.S. FDA in March 2011 for treatment of patients with active, autoantibody-positive, systemic lupus erythematosus (SLE). Belimumab is a human sequence monoclonal antibody that binds to human B lymphocyte stimulator protein (BLys; also known as BAFF, THANK, TALL-1, TNFSF13B, and zTNF4), which is overexpressed in SLE patients. BLys is expressed on the cell surface of monocytes, macrophages, and monocyte-derived dendritic cells and is cleaved to form a soluble cytokine that stimulates cell proliferation and antibody secretion in B lineage cells that express the BLys receptor BAFF-R (also known as BR-3). The precise function of two additional BLys receptors, TACI and BCMA, is less clear. Belimumab inhibits BLys interaction with these three receptors leading to measurable reductions in autoantibodies, such as anti-dsDNA, and specific circulating B cell lineage compartments including antibody producing plasma cells. Belimumab was discovered by screening molecules from a phage display library of human single-chain Fv sequences for BLys binding and functional blocking, followed by optimization of the lead through the introduction of variant residues in V_H CDR3.

Originator

Human Genome Sciences (United States)

Uses

Treatment of autoimmune disease.

brand name

LymphoStat-B (Human Genome Sciences);Benlysta.

Clinical Use

Anti-lymphocyte monoclonal antibody:

Treatment of systemic lupus erythematosus

Drug interactions

Potentially hazardous interactions with other drugs
Live vaccines: avoid concomitant use.

Metabolism

Belimumab is a protein for which the expected metabolic pathway is degradation to small peptides and individual amino acids by widely distributed proteolytic enzymes. Classical biotransformation studies have not been conducted.

Raw materials

Preparation Products