Ofatumumab

Ofatumumab, sold under the brand name Arzerra among others, is a fully human monoclonal antibody to CD20, 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 (Campath) and for the treatment of multiple sclerosis. It has also shown potential in treating follicular lymphoma, diffuse large B cell lymphoma, rheumatoid arthritis. Ofatumumab is 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.
The most common side effects for ofatumumab (Arzerra) include infusion reactions and neutropenia. The most common side effects for ofatumumab (Kesimpta) include upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions.
Medical uses.
Ofatumumab is indicated for the treatment of untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL).
In the United States and the European Union it is also indicated for the treatment of relapsing forms of multiple sclerosis in adults.
Adverse effects.
Adverse effects by frequency:<br>
Very common (>10% frequency):
Common (1-10% frequency):'
Uncommon (0.1-1% frequency):
Rare (<0.1% frequency):
Ofatumumab has received a black box warning regarding the potential for it to cause progressive multifocal leukoencephalopathy and hepatitis B reactivation. Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.
Interactions.
No formal drug interaction studies have been conducted with ofatumumab. Although it is advised that patients are not administered live virus vaccines (e.g. the oral polio vaccine) while undergoing treatment with ofatumumab due to the compromised ability to fight the attenuated viruses seen in patients being treated with ofatumumab.
Mechanism.
Ofatumumab is a human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab. The CD20 antigen is expressed on solely B cell lymphocytes. Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate. It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).
History.
Ofatumumab (Arzerra) was approved for medical use in the United States in October 2009.
Ofatumumab (Arzerra) was approved for medical use in the European Union in June 2010, and for use in Canada in August 2012. It was approved for use in the UK in April 2010.
For commercial reasons, Ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017. It was withdrawn from the European Union in February 2019. Novartis removed it from all of the non-US markets and made it available only for compassionate use in those markets.
Ofatumumab (Kesimpta) was approved for medical use in the United States in August 2020. Novartis applied for European approval via the European Medicines Agency (EMA) in early 2020 with an evaluation expected in Q2 of 2021. On 28 January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kesimpta, intended for the treatment of adults with active relapsing forms of multiple sclerosis. The applicant for this medicinal product is Novartis Ireland Limited. Ofatumumab (Kesimpta) was approved for medical use in the European Union in March 2021.
Society and culture.
Economics.
Ofatumumab (Arzerra) was transitioned to an oncology access program to make it available at no cost to chronic lymphocytic leukemia patients in the U.S.