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| Molar mass | 71 kg/mol |
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Atacicept is arecombinant fusion protein designed to inhibitB cells, thereby suppressingautoimmune disease. The designer protein combines the binding site for twocytokines that regulate maturation, function, and survival of B cells –B-lymphocyte stimulator (BLyS) andA proliferation-inducing ligand (APRIL), with the constant region ofimmunoglobin.[1] Atacicept blocks activation of B cells by the tumor necrosis factor receptor superfamily member 13B (more commonly known asTACI), a transmembrane receptor protein found predominantly on the surface of B cells. Like themonoclonal antibodybelimumab, atacicept blocks the binding of BLyS, but it also blocks APRIL. Binding of these TACI ligands induces proliferation, activation, and longevity of B cells and thus their production ofautoantibodies.[2] Atacicept is thought to selectively impair mature B cells and plasma cells with less impact onprogenitor cells andmemory B cells.[3]
Studies have looked at atacicept in animal models of autoimmune disease and in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and optic neuritis.[4] A phase II/III trial forsystemic lupus erythematosus is due to run from 2008 to 2012.[5] The subcutaneously injected protein failed a phase II trial formultiple sclerosis.[6] The trials of atacicept in people with MS were suspended when some people taking the drug in one trial had an unexpected increase in inflammatory activity. An independent data monitoring board for the MS study found "subjects receiving atacicept were having more relapses and new MRI lesions than those on the placebo."[7]
The drug is also being studied for treatment of B-cell malignancies, includingmultiple myeloma,B-cell chronic lymphocytic leukemia, andnon-Hodgkin's lymphoma.[4]
Atacicept was developed by a Seattle-based biotech company, ZymoGenetics, which handed the product over to Merck Serono for further development.[8]