Blisibimod

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.^[1] It is currently under active investigation in clinical trials.^[2]

Blisibimod

Clinical data
Other names	A-623
ATC code	none
Legal status
Legal status	Investigational
Identifiers
CAS Number	1236126-45-6 N
ChemSpider	none
UNII	114VP6C6ES
KEGG	D10311 N
Chemical and physical data
Formula	C2836H4376N756O858S26
Molar mass	63624.20 g·mol−1
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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.^[1]

BAFF is involved in B-cell survival, activation, and differentiation.^[3] Elevated levels of BAFF have been associated with several B-cell mediated autoimmune diseases, including systemic lupus erythematosus,^[4][5][6] lupus nephritis,^[7] rheumatoid arthritis,^[5][6] multiple sclerosis,^[8] Sjögren syndrome,^[9] Graves' disease,^[10] and Hashimoto's thyroiditis.^[10] Blisibimod binds to BAFF and inhibits interaction with BAFF receptors, thus decreasing B-cell survival and proliferation throughout the body.^[1][3] Improvements in disease activity have been observed in patients with systemic lupus erythematosus^[11] and rheumatoid arthritis^[12] 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.^[1] It was subsequently acquired by Anthera Pharmaceuticals,^[13] 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.^[2][14] The PEARL-SC study, completed in April 2012, yielded data that has been published.^[15] 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.