Blisibimod

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Blisibimod
Clinical data
Other namesA-623
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  • Investigational
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Chemical and physical data
Formula C2836H4376N756O858S26
Molar mass 63624.20 g·mol−1
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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]

Contents

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.

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References

  1. 1 2 3 4 "A-623: BAFF Peptibody for the Treatment of Lupus". Anthera Pharmaceuticals, Inc. Archived from the original on 2011-09-02. Retrieved 2011-07-08.
  2. 1 2 "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. Archived from the original on 3 June 2011. Retrieved 15 July 2011.
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