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.
It is currently under active investigation in clinical trials.
Mechanism of action
Blisibimod is a
fusion protein 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 of the
fragment crystallizable region (Fc) of a human
antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
.
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
Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. Since it is a result of SLE, this type of glomerulo ...
,
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...
,
,
,
,
and
Hashimoto's thyroiditis
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...
.
Blisibimod binds to BAFF and
inhibits interaction with BAFF
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
, 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 company headquartered in Thousand Oaks, California. One of the world's largest independent biotechnology companies, Amgen was established in T ...
, with
Phase I trials demonstrating comparable safety between the blisibimod and
placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures.
In general, placebos can af ...
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 disease of the kidney (or nephropathy) and the immune system; specifically it is a form of glomerulonephritis or an inflammati ...
.
References
{{Cytokine receptor modulators
Engineered proteins