Ofatumumab

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 binding of monoclonal antibodies to CD20 results in recruitment of immunological devices that trigger cytotoxic events, such as compliment-dependent cytotoxicity (CDC). CDC is the major natural immune response in the body triggered by antibody binding, used to eliminate invading or dysfunctional pathogenic cells.^[5] Ofatumumab is an anti-CD20 human monoclonal antibody which binds a unique epitope on CD20 with high specificity. This epitope is membrane proximal compared to the epitope of Rituximab, which might explain Ofatumumab's increased potency compared to that of Rituximab. Further, because the epitope of Ofatumumab includes a small extracellular loop of CD20 and binds very tightly resulting in a slow off-rate, this too may explain Ofatumumab's increased CDC potency.^[6]