Ofatumumab

Ofatumumab (trade name Arzerra, also known as HuMax-CD20) is a human monoclonal antibody (for the CD20 protein) which appears to inhibit early-stage B lymphocyte activation. It is FDA approved for treating chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab and has also shown potential in treating follicular non-Hodgkin’s lymphoma, diffuse large B cell lymphoma, rheumatoid arthritis and relapsing remitting multiple sclerosis. Ofatumumab has also received conditional approval in Europe for the treatment of refractory chronic lymphocytic leukemia. This makes ofatumumab the first marketing application for an antibody produced by Genmab, as well as the first human monoclonal antibody which targets the CD20 molecule that will be available for patients with refractory CLL.

Mechanism
Ofatumumab targets an epitope different from rituximab and most other CD20 directed antibodies. Ofatumumab binds to both the small and large loops of the CD20 molecule on B cells. Its location is in closer proximity to the membrane, which in theory allows for more effective complement deposition and subsequent B cell killing. The CD20 molecule is highly expressed in both normal and malignant B cells.

Approvals and indications
It was approved by FDA in Oct 2009 for chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab. It was conditionally approved by the EMA for refractory chronic lymphocytic leukemia in 2010.

Clinical trials
Status of clinical trials of ofatumumab conducted by Genmab and GSK, as of late 2010.
 * Relapsed follicular non-Hodgkin's lymphoma (NHL)-Phase III
 * Rheumatoid arthritis (RA):
 * Phase III – OFA110635/GEN410 – Ofatumumab in adult RA patients who have had an inadequate response to methotrexate
 * Phase III – OFA110634/GEN411 – Ofatumumab in adult RA patients who have had an inadequate response to TNF-alpha antagonist therapy
 * Diffuse large B cell lymphoma (DLBCL) – Phase III
 * B-cell chronic lymphocytic leukemia (B-CLL) – Phase III
 * Waldenstrom's Macroglobulinemia - Phase II
 * Relapsing Remitting Multiple Sclerosis (RRMS)-Phase II
 * Mantle cell lymphoma (MCL)