Blisibimod

Mechanism of action

Blisibimod is a fusion protein consisting of four BAFF binding domains fused to the N-terminus of the fragment crystallizable region (Fc) of a human antibody.

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 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.

Development

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 published. 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.

References

References

1. "A-623: BAFF Peptibody for the Treatment of Lupus". Anthera Pharmaceuticals, Inc..
2. (29 July 2010). "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)". Anthera Pharmaceuticals, Inc..
3. (July 2006). "B cells move to centre stage: novel opportunities for autoimmune disease treatment". Nature Reviews. Drug Discovery.
4. (August 2008). "Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus". Arthritis and Rheumatism.
5. (June 2001). "Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases". Arthritis and Rheumatism.
6. (January 2001). "Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus". Journal of Immunology.
7. (January 2011). "Intrarenal production of B-cell survival factors in human lupus nephritis". Modern Pathology.
8. (January 2005). "BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma". The Journal of Experimental Medicine.
9. (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.
10. (January 2010). "BLyS and April serum levels in patients with autoimmune thyroid diseases". Autoimmunity Reviews.
11. (February 2011). "Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial". Lancet.
12. (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.
13. (2008-01-08). "Anthera Pharmaceuticals acquires the worldwide rights to a BAFF inhibitor for the treatment of lupus and other autoimmune diseases.". Anthera Pharmaceuticals, Inc..
14. {{ClinicalTrialsGov. NCT01162681. PEARL-SC Trial: A Study of the Efficacy, Safety, and Tolerability of A 623 Administration in Subjects With Systemic Lupus Erythematosus
15. (September 2015). "A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study". Annals of the Rheumatic Diseases.