Belimumab (Benlysta) is a human IgG1 monoclonal antibody directed at BLyS (B lymphocyte stimulatory protein; also called BAFF, TNFSF13B, THANK, TALL-1, and neutrokine-a). Belimumab blocks the binding of BLyS to each of its three receptors on B cells: BCMA, TACI and BR3, and thereby inhibits the proliferation and differentiation of B cells. Since in vivo therapy results in only a modest apparent depletion of B cells, the exact mechanism of the therapeutic effects of belimumab is not evident.
Belimumab is administered by monthly intravenous infusions. An efficacy and safety study for the use of belimumab administered as subcutaneous route appears promising.
When belimumab was approved by the FDA in 2011, it was the first drug that received an indication for lupus in over three decades. The approval was based on two successful large (for lupus) phase III trials, each with >800 patients, using a composite clinical endpoint. It is indicated for the treatment of patients with active SLE in combination with standard therapy. Its efficacy in patients with severe renal or central nervous system lupus has not been tested but are underway for lupus nephritis. Belimumab showed encouraging results in open-label phase II study of patients with primary Sjogren’s syndrome.
Based on the clinical trials, belimumab appears to be generally well tolerated, although safety concerns were raised for hypersensitivity, infections, depression, and overall mortality.