Ofatumumab
Encyclopedia
Ofatumumab 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.
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.
that is refractory to fludarabine and alemtuzumab. It was conditionally approved by the EMA for refractory chronic lymphocytic leukemia in 2010.
, as of late 2010.
Human
Humans are the only living species in the Homo genus...
monoclonal antibody (for the CD20
CD20
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
protein) which appears to inhibit early-stage B lymphocyte activation. It is FDA approved for treating chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
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
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
and relapsing remitting multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. 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
Genmab
Genmab A/S is a Danish biotechnology company, founded in February 1999 and based in Copenhagen. Internationally, it operates through the subsidiaries Genmab BV in Utrecht, The Netherlands, and Genmab, Inc in Princeton, New Jersey, USA. The Company is publicly traded on the NASDAQ OMX Copenhagen A/S...
, 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 epitopeEpitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
different from rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
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 leukemiaChronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
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 GSKGlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
, as of late 2010.
-
- Relapsed follicular non-Hodgkin's lymphoma (NHL)-Phase III
- Rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
(RA):- Phase III – OFA110635/GEN410 – Ofatumumab in adult RA patients who have had an inadequate response to methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
- Phase III – OFA110634/GEN411 – Ofatumumab in adult RA patients who have had an inadequate response to TNF-alpha antagonist therapy
- Phase III – OFA110635/GEN410 – Ofatumumab in adult RA patients who have had an inadequate response to methotrexate
- Diffuse large B cell lymphomaDiffuse large B cell lymphomaDiffuse large B-cell lymphoma is a type of aggressive non-Hodgkin lymphoma. It accounts for approximately 40% of lymphomas among adults. The median age at diagnosis is 70 years, but it also occurs in children and young adults...
(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 lymphomaMantle cell lymphomaMantle cell lymphoma is one of the rarest of the non-Hodgkin's lymphomas , comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. While it is difficult to treat and seldom considered cured, investigations into better treatments are actively pursued worldwide...
(MCL)
See also
- RituximabRituximabRituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, a chimerical anti-CD20 antibody - OcrelizumabOcrelizumabOcrelizumab is a humanized anti-CD20 monoclonal antibody. It targets mature B lymphocytes and hence is an immunosuppressive drug candidate. It is under development by Hoffmann–La Roche's subsidiary Genentech, and Biogen Idec....
, a humanized (90%) anti-CD20 antibody