|14px (what is this?)|
Blisibimod (also known as A-623, formerly AMG 623) is a selective antagonist of B-cell activating factor (BAFF, also known as B-lymphocyte stimulator or BLyS), being developed by Anthera Pharmaceuticals as a treatment for systemic lupus erythematosus. It is currently under active investigation in clinical trials.
BAFF is involved in B-cell survival, activation, and differentiation. Elevated levels of BAFF have been associated with several B-cell mediated autoimmune diseases, including systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, multiple sclerosis, Sjögren’s syndrome, Graves’ disease, and Hashimoto's thyroiditis. Blisibimod binds to BAFF and inhibits interaction with BAFF receptors, thus decreasing B-cell survival and proliferation throughout the body. Improvements in disease activity have been observed in patients with systemic lupus erythematosus and rheumatoid arthritis following treatment with BAFF inhibitors in clinical trials.
Blisibimod was initially developed by Amgen, with Phase I trials demonstrating comparable safety between the blisibimod and placebo treatments. It was subsequently acquired by Anthera Pharmaceuticals, who in 2010 initiated a global Phase II study called PEARL-SC to investigate the efficacy, safety, and tolerability of blisibimod in subjects with systemic lupus erythematosus. The PEARL-SC study, completed in April 2012, yielded data that has been presented at several nephrology-centered conferences, including ACR and EULAR. Blisibimod is currently being tested in a Phase 3 study, CHABLIS-SC1, for Systemic Lupus Erythematosus, and a Phase 2 study, BRIGHT-SC, for IgA nephropathy.
- "A-623: BAFF Peptibody for the Treatment of Lupus". Anthera Pharmaceuticals, Inc. Retrieved 2011-07-08.
- "Anthera Initiates Expanded and Extended PEARL-SC Phase 2b Clinical Study in Lupus With A-623 - A Subcutaneous Dual Inhibitor of Membrane and Soluble B-Cell Activating Factor (BAFF or BLyS)" (Press release). Anthera Pharmaceuticals, Inc. 29 July 2010.
- Browning, J.L. (July 2006). "B cells move to centre stage: novel opportunities for autoimmune disease treatment.". Nature Reviews Drug Discovery 5 (7): 564–76. PMID 16816838. doi:10.1038/nrd2085.
- Petri, P.; Stohl, W.; Chatham, W.; McCune, W.J.; Chevrier, M.; Ryel, J.; Recta, V.; Zhong, J.; Freimuth, W. (August 2008). "Association of plasma b lymphocyte stimulator levels and disease activity in systemic lupus erythematosus". Arthritis & Rheumatism 58 (8): 2453–9. PMID 18668552. doi:10.1002/art.23678.
- Cheema, G.S.; Roschke, V.; Hilbert, D.M.; Stohl, W. (June 2001). "Elevated serum b lymphocyte stimulator levels in patients with systemic immune–based rheumatic diseases". Arthritis & Rheumatism 44 (6): 1313–9. PMID 11407690. doi:10.1002/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S.
- Zhang, J.; Roschke, V.; Baker, K.P.; Wang, Z.; Alarcon, G.S.; Fessler, B.J.; Bastian, H.; Kimberly, R.P.; Zhou, T. (January 2001). "Cutting edge: a role for b lymphocyte stimulator in systemic lupus erythematosus". Journal of Immunology 166 (1): 6–10. PMID 11123269. doi:10.4049/jimmunol.166.1.6.
- Neusser, M.A.; Lindenmeyer, M.T.; Edenhofer, I.; Gaiser, S.; Kretzler, M.; Regele, H.; Segerer, S.; Cohen, C.D. (January 2011). "Intrarenal production of b-cell survival factors in human lupus nephritis.". Modern Pathology 24 (1): 98–107. PMID 20890272. doi:10.1038/modpathol.2010.184.
- Krumbholz, M.; Theil, D.; Derfuss, T.; Rosenwald, A.; Schrader, F.; Monoranu, C.M.; Kalled, S.L.; Hess, D.M.; Seraﬁni, B.; Aloisi, F.; Wekerle, H.; Hohlfeld, R.; Meinl, E. (January 2005). "BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma.". Journal of Experimental Medicine 201 (2): 195–200. PMC 2212784. PMID 15642740. doi:10.1084/jem.20041674.
- Quartuccio, L.; Fabris, M.; Moretti, M.; Barone, F.; Bombardieri, M.; Rupolo, M.; Lombardi, S.; Pitzalis, C.; Beltrami, C.A.; Curcio, F.; De Vita, S. (2008). "Resistance to rituximab therapy and local BAFF overexpression in sjögren’s syndrome-related myoepithelial sialadenitis and low-grade parotid b-cell lymphoma.". The Open Rheumatology Journal 2: 38–43. PMC 2577948. PMID 19088870. doi:10.2174/1874312900802010038.
- Fabris, M.; Grimaldi, F.; Villalta, D.; Picierno, A.; Fabro, C.; Bolzan, M.; De Vita, S.; Tonutti, E. (January 2010). "BLyS and april serum levels in patients with autoimmune thyroid diseases.". Autoimmunity Reviews 9 (3): 165–9. PMID 19647102. doi:10.1016/j.autrev.2009.07.005.
- Navarra, S.V.; Guzmán, R.M.; Gallacher, A.E.; Hall, S.; Levy, R.A.; Jimenez, R.E.; Li, E.K.M.; Thomas, M.; Kim, H.; León, M. G.; Tanasescu, C.; Nasonov, E.; Lan, J.L.; Pineda, L.; Zhong, Z.J.; Freimuth, W.; Petri, M.A. (February 2011). "Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial.". The Lancet 377 (9767): 721–31. PMID 21296403. doi:10.1016/S0140-6736(10)61354-2.
- Genovese, M.C.; Bojin, S.; Biagini, M.; Mociran, E.; Cristei, D.; Georgescu, L.; Sloan-Lancaster, J. (June 2010). "Effects on b cells, safety, and efficacy of LY2127399, a novel anti-BAFF MAB, in patients with active rheumatoid arthritis.". Annals of the Rheumatic Diseases 69 (Suppl3): 69.
- "Anthera Pharmaceuticals acquires the worldwide rights to a BAFF inhibitor for the treatment of lupus and other autoimmune diseases." (Press release). Anthera Pharmaceuticals, Inc. 2008-01-08.
- ClinicalTrials.gov. "PEARL-SC Trial: A Study of the Efficacy, Safety, and Tolerability of A 623 Administration in Subjects With Systemic Lupus Erythematosus.". United States National Institute of Health. Retrieved 2011-07-15.
- "Anthera Announces Additional Data from the Phase 2b PEARL-SC Presented at the ACR/ARHP 2012 Annual Scientific Meeting" (Press release). Anthera Pharmaceuticals, Inc. 2012-11-13.
- "Anthera Pharmaceuticals to Present at Annual Jefferies Healthcare Conference" (Press release). Anthera Pharmaceuticals, Inc. 2013-05-07.