Ofatumumab is a fully human monoclonal antibody to

CD20 B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase ( CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene ...

, which appears to provide rapid B-cell depletion. Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the European Union and other regions. Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States. It is sold by

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

under license from

Genmab Genmab A/S is a Danish biotechnology company, founded in February 1999 by Florian Schönharting, at the time managing director of BankInvest Biomedical venture fund. The company is based in Copenhagen, Denmark - internationally, it operates thr ...

. The most common side effects for ofatumumab (Kesimpta) include

upper respiratory tract infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the nose, sinuses, pharynx, larynx or trachea. This commonly includes nasal obstruction, sore thro ...

, headache, injection-related reactions, and local

injection site reaction Injection site reactions are allergic reactions that result in cutaneous necrosis that may occur at sites of medication injection, typically presenting in one of two forms, (1) those associated with intravenous infusion or (2) those related to intra ...

s. The most common side effects for ofatumumab (Arzerra) include infusion reactions and neutropenia.

Medical uses

Ofatumumab (Kesimpta 20 mg solution for injection in pre-filled syringe/pen) is indicated for the treatment of relapsing forms of multiple sclerosis in adults. The recommended dose is 20 mg of ofatumumab administered by subcutaneous injection with monthly dosing following loading. Treatment with ofatumumab has been shown to rapidly deplete B-cells which aids MS pathogenesis by influencing and regulating different autoimmune process such as T-cell production and APC activity. Depleted B-cells are required to address chronic clinical conditions like MS. Ofatumumab (Arzerra 100 mg or 1000 mg concentrate for solution for infusion) is indicated for the treatment of untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL). The recommended doses for treatment of CLL are higher than MS, with 1000 or 2000 mg infusions administered monthly depending on if the CLL is untreated, relapsed or refractory, following loading. Ofatumumab is under investigation as a potential treatment for

follicular lymphoma Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells norma ...

, diffuse large B cell lymphoma and

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

Adverse effects

Adverse effects of ofatumumab (Kesimpta) by frequency: Very common (>10% frequency): * Upper respiratory tract infection * Injection-related reactions (systemic) * Injection-site reactions (local) * Urinary tract infections * Headache Common (1-10% frequency): * Backpain * Blood immunoglobulin M decreased * Oral herpes Adverse effects of ofatumumab (Arzerra) by frequency:
Very common (>10% frequency): * Lower respiratory tract infection, including

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...

* Upper respiratory tract infection * Rash *

Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

* Neutropenia * Dyspneoa * Cough * Nausea * Diarrhoea * Pyrexia * Fatigue * Bronchitis Common (1-10% frequency):' * Cytopnia *

Sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

* Infusion reaction * Herpes virus infection *

Urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

* Febrile neutropenia *

Leucopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

Thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...

* Anaphylactoid reactions * Hypersensitivity * Headache *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

* Hypotension * Hypertension * Bronchospasm * Hypoxia * Chest discomfort * Pharyngolaryngeal pain * Nasal congestion * Small bowel obstruction * Itchiness * Flushing * Back pain * Cytokine release syndrome * Rigors * Chills * Hyperhidrosis Uncommon (0.1-1% frequency): * Agranulocytosis * Bradycardia * Hepatitis B infection and reactivation * Coagulopathy * Red cell aplasia *

Lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which ...

* Anaphylactic reactions *

Tumour lysis syndrome Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...

Rare (<0.1% frequency): *

Hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...

infection or reactivation Ofatumumab (Arzerra) has received a

black box warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that it ...

regarding the potential for it to cause progressive multifocal leukoencephalopathy and

hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...

reactivation. Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection. For more information, please refer to the prescribing information or your doctor.

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. While on treatment with ofatumumab (Kesimpta), all immunizations should be administered according to immunization guidelines at least 4 weeks prior to initiation of ofatumumab for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ofatumumab for inactivated vaccines.

Mechanism

Ofatumumab is a fully human anti-

monoclonal antibody whose epitope is distinct from that of

rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric pa ...

. Ofatumumab binds to a distinct epitope on small and large extracellular loops of CD20. 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 Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. When they are bound to surface antigen on target cell (e.g. bacterial or viral infected cell), the classical complement pathway is triggered by bonding prot ...

(CDC) and

antibody-dependent cellular cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose ...

(ADCC).

History

Ofatumumab was jointly developed by Danish biotech Genmab and GlaxoSmithKline

GSK plc GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

who entered into an agreement to co-develop and commercialize ofatumumab in 2006. It was approved as Arzerra for the treatment of chronic lymphocytic leukemia in the United States in October 2009. Ofatumumab (Arzerra) was then approved in the European Union in June 2010, in the United Kingdom in April 2010, and in Canada in August 2012. In 2014, Novartis acquired a number of GSK’s oncology products, including the collaboration with Genmab and ofatumumab. 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 the treatment of relapsing forms of multiple sclerosis in adults in the United States in August 2020. EU approval was subsequently received 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.

References

External links

* * {{Portal bar , Medicine Monoclonal antibodies for tumors Breakthrough therapy GSK plc brands Novartis brands Withdrawn drugs