Atacicept
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| Molar mass | 71 kg/mol |
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Atacicept is a recombinant fusion protein designed to inhibit B cells, thereby suppressing autoimmune disease. The designer protein combines the binding site for two cytokines that regulate maturation, function, and survival of B cells - B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL), with the constant region of immunoglobin.[1] Atacicept blocks activation of B cells by the tumor necrosis factor receptor superfamily member 13B (more commonly known as TACI), a transmembrane receptor protein found predominantly on the surface of B cells. Like the monoclonal antibody belimumab, 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 of autoantibodies.[2] Atacicept is thought to selectively impair mature B cells and plasma cells with less impact on progenitor cells and memory 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 for systemic lupus erythematosus is due to run from 2008 to 2012.[5] The subcutaneously injected protein failed a phase II trial for multiple 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, including multiple myeloma, B-cell chronic lymphocytic leukemia, and non-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]
References
[edit]- ^ Hartung HP, Kieseier BC (July 2010). "Atacicept: targeting B cells in multiple sclerosis". Therapeutic Advances in Neurological Disorders. 3 (4): 205–16. doi:10.1177/1756285610371146. PMC 3002656. PMID 21179612.
- ^ Stuart (14 January 2009). "Merck Serono and ZymoGenetics Initiate Atacicept Phase 2 Clinical Trial in Relapsing Multiple Sclerosis". Wellsphere. Archived from the original on 2010-08-23.
- ^ Nestorov I, Munafo A, Papasouliotis O, Visich J (April 2008). "Pharmacokinetics and biological activity of atacicept in patients with rheumatoid arthritis". Journal of Clinical Pharmacology. 48 (4): 406–17. doi:10.1177/0091270008315312. PMID 18303125. S2CID 11540779.
- ^ a b Vasiliou S (2008). "Atacicept". Drugs of the Future. 33 (11): 921. doi:10.1358/dof.2008.033.011.1281855. S2CID 258504455.
- ^ Clinical trial number NCT00624338 for "Atacicept Phase II/III in Generalized Systemic Lupus Erythematosus (April SLE) " at ClinicalTrials.gov
- ^ Clinical trial number NCT00642902 for "Atacicept in Multiple Sclerosis, Phase II" at ClinicalTrials.gov
- ^ Hollie (1 October 2009). "More drug news - two oral drugs making progress, but atacicept trial stopped". MSNews. Archived from the original on 2010-10-29.
- ^ Timmerman L (3 September 2008). "ZymoGenetics Hands Over Atacicept Rights to Partner, Merck KGaA. The Darmstadt, Germany-based Merck KGaA".