Belimumab

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Compound Name:BelimumabMolecular Target:BLyS (B-lymphocyte stimulator)Molecular Structure:Human monocolonal antibody IgG1-lambdaLicensed Indication:Systematic lupus erythematosusManufacturer and/or Distributor:Human Genome Sciences/ GlaxoSmithKlineInitial FDA Approval2011SummaryBelimumab (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.References

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1. Stohl W, Scholz JL, Cancro MP. Targeting BLyS in rheumatic disease: the sometimes-bumpy road from bench to bedside. Curr Opin Rheumatol. 2011 May;23(3):305-310.
http://www.ncbi.nlm.nih.gov/pubmed/21330926

2. Ding C. Belimumab, an anti-BLyS human monoclonal antibody for potential treatment of inflammatory autoimmune diseases. Expert Opin Biol Ther. 2008 Nov;8(11):1805-1814.
http://www.ncbi.nlm.nih.gov/pubmed/18847314

3. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzova D, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011 Dec;63(12):3918-3930.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22127708

4. Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb 26;377(9767):721-731.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21296403

5. Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum. 2009 Sep 15;61(9):1168-1178.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19714604

6. Cancro MP, D'Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest. 2009 May;119(5):1066-1073.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19411764

7. Mariette X, Seror R, Quartuccio L, Baron G, Salvin S et al. Efficacy and safety of belimumab in primary Sjogren's syndrome: results of the BELISS open-label phase II study. Ann Rheum Dis. 2013 Dec 17. http://www.ncbi.nlm.nih.gov/pubmed/24347569

8. Ginzler EM, Wallace DJ, Merrill JT, Furie RA, Stohl W, Chatham WW, Weinstein A, McKay JD, McCune WJ, Zhong ZJ, Freimuth WW, Petri MA; LBSL02/99 Study Group. Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol. 2014 Feb;41(2):300-9. http://www.ncbi.nlm.nih.gov/pubmed/24187095

9. Aytan J, Bukhari MA. Use of biologics in SLE: a review of the evidence from a clinical perspective. Rheumatology (Oxford). 2015 Sep 30. http://www.ncbi.nlm.nih.gov/pubmed/26424838

10. Narain S, Furie R. Curr Opin Rheumatol. 2016 Sep;28(5):477-87. doi: 10.1097/BOR.0000000000000311. Update on clinical trials in systemic lupus erythematosus. https://www.ncbi.nlm.nih.gov/pubmed/27314466

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