Blisibimod (also known as A-623, formerly AMG 623) is a selective antagonist of

B-cell activating factor B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B and CD257 among other names, is a protein that in humans is encoded by the ''TNFSF13B'' gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) a ...

(BAFF, also known as B-lymphocyte stimulator or BLyS), being developed by Anthera Pharmaceuticals as a treatment for

systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

. It is currently under active investigation in clinical trials.

Mechanism of action

Blisibimod is a

fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...

consisting of four BAFF

binding domains In molecular biology, binding domain is a protein domain which binds to a specific atom or molecule, such as calcium or DNA. A protein domain is a part of a protein sequence and a tertiary structure that can change or evolve, function, and live ...

fused to the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

of the

fragment crystallizable region The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This region allows antibodies to activate the immune s ...

(Fc) of a human

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

. BAFF is involved in

B-cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

survival, activation, and differentiation. Elevated levels of BAFF have been associated with several B-cell mediated

autoimmune diseases An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that ...

, including systemic lupus erythematosus,

lupus nephritis Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE) and childhood-onset systemic lupus erythematosus which is a more severe form of SLE that develops in children up to 18 years old; both are autoimmune d ...

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

Sjögren syndrome Sjögren is a Swedish surname. Notable people with the surname include: * Anders Johan Sjögren (1794–1855), Finnish linguist, historian, ethnographer and explorer * Ann Mari Sjögren, Swedish fantasy artist and illustrator * Christer Sjögren, ...

Graves' disease Graves' disease, also known as toxic diffuse goiter or Basedow's disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...

, and

Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, Hashimoto's disease and autoimmune thyroiditis, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over ti ...

. Blisibimod binds to BAFF and inhibits interaction with BAFF

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

, 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 Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical Corporation, company headquartered in Thousand Oaks, California. As one of the world's largest independent biotechnology companies, Amgen has a ...

, with Phase I trials demonstrating comparable safety between the blisibimod and

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

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 IgA nephropathy (IgAN), also known as Berger's disease () (and variations), or synpharyngitic glomerulonephritis, is a kidney disease, disease of the kidney (or nephropathy) and the immune system; specifically it is a form of glomerulonephritis o ...

References

{{Cytokine receptor modulators Engineered proteins