Ofatumumab
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Better Known as: Arzerra
- Marketed By: Genmab & GlaxoSmithKline
- Major Indications: Chronic Lymphocytic Leukemia & Rheumatoid Arthritis
- Drug Class: Anti-CD20 Monoclonal Antibody
- Date of FDA Approval (Patent Expiration): 2009 (2023)
- 2010 Sales: $60 Million
- Importance: Recieved accelerated approval by the FDA for treatment of Chronic Lymphocytic Leukemia. Targets a different CD20 epitope than Rituximab. This epitope is located closer to the cell membrane, which should allow for more effective complement deposition and subsequent cancerous B-Cell killing. Numerous studies validated this increased cytotoxicity. Further, Ofatumumab dissociates from its target at a slower rate compared to Rituximab. Currently being tested for efficacy in a number of phase II and III trials for B-Cell Lymphoma and Rheumatoid Arthritis as well as Multiple Sclerosis.[1][2]
- See Pharmaceutical Drugs for more information about other drugs and diseases.
Mechanism of Action
Chronic Lymphocytic Leukemia & Rheumatoid Arthritis are diseases associated with B-cell dysfunction. B-cells play a key role in the humoral immune system by acting as antigen-presenting cells (which activate T-cells) and by eventually producing antibodies against invading antigens.[3] Although the function of B-Lymphocyte Antigen CD20 has not yet been determined, and in fact knockout mice which do not produce CD20 are healthy, CD20 is expressed on almost all normal and malignant B-cells.[4] A number of studies have demonstrated that the crosslinking of CD20 with monoclonal antibodies can recruit immunological devices that trigger cytotoxic events, such as antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC).[5]
References
- ↑ Coiffier B, Lepretre S, Pedersen LM, Gadeberg O, Fredriksen H, van Oers MH, Wooldridge J, Kloczko J, Holowiecki J, Hellmann A, Walewski J, Flensburg M, Petersen J, Robak T. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008 Feb 1;111(3):1094-100. Epub 2007 Nov 14. PMID:18003886 doi:10.1182/blood-2007-09-111781
- ↑ Zhang B. Ofatumumab. MAbs. 2009 Jul-Aug;1(4):326-31. Epub 2009 Jul 1. PMID:20068404
- ↑ Montecino-Rodriguez E, Dorshkind K. New perspectives in B-1 B cell development and function. Trends Immunol. 2006 Sep;27(9):428-33. Epub 2006 Jul 24. PMID:16861037 doi:10.1016/j.it.2006.07.005
- ↑ Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005;8:140-74. PMID:15564720 doi:10.1159/000082102
- ↑ Zhang B. Ofatumumab. MAbs. 2009 Jul-Aug;1(4):326-31. Epub 2009 Jul 1. PMID:20068404