Monoclonal antibody | |
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Type | Whole antibody |
Source | Human |
Target | CD20 |
Clinical data | |
Trade names | Arzerra, Kesimpta |
Other names | HuMax-CD20, OMB157 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a621050 |
License data |
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Pregnancy category | |
Routes of administration | Intravenous (Arzerra), subcutaneous (Kesimpta) |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Elimination half-life | 14 days |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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UNII | |
KEGG | |
ChEMBL | |
Chemical and physical data | |
Formula | C6480H10022N1742O2020S44 |
Molar mass | 146062.27 g·mol−1 |
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Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion. [12] 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. [8] [10] Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States. [13] It is sold by Novartis under license from Genmab. [14]
The most common side effects for ofatumumab (Kesimpta) include upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions. [8] The most common side effects for ofatumumab (Arzerra) include infusion reactions and neutropenia. [13]
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. [8] [10] [15] The recommended dose is 20 mg of ofatumumab administered by subcutaneous injection with monthly dosing following loading. [16] [17]
Treatment with ofatumumab has been shown to rapidly deplete B-cells [16] [17] which aids MS pathogenesis by influencing and regulating different autoimmune process such as T-cell production and APC activity. [18] 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). [7] [19] [4] [20] 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. [20]
Ofatumumab is under investigation as a potential treatment for follicular lymphoma, diffuse large B cell lymphoma and rheumatoid arthritis.[ citation needed ]
Adverse effects of ofatumumab (Kesimpta) by frequency: [21] [17]
Very common (>10% frequency):
Common (1-10% frequency):
Adverse effects of ofatumumab (Arzerra) by frequency: [7] [13] [4]
Very common (>10% frequency):
Common (1-10% frequency):'
Uncommon (0.1-1% frequency):
Rare (<0.1% frequency):
Ofatumumab (Arzerra) has received a black box warning regarding the potential for it to cause progressive multifocal leukoencephalopathy and hepatitis B reactivation. [15] [22] Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection. [22]
For more information, please refer to the prescribing information or your doctor.
No formal drug interaction studies have been conducted with ofatumumab. [7] 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. [22] 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. [21]
Ofatumumab is a fully human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab. [23] Ofatumumab binds to a distinct epitope on small and large extracellular loops of CD20. [24] [25] The CD20 antigen is expressed on solely B cell lymphocytes. [23] Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate. [23] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). [23]
Ofatumumab was jointly developed by Danish biotech Genmab and GlaxoSmithKline GSK plc who entered into an agreement to co-develop and commercialize ofatumumab in 2006. [26] It was approved as Arzerra for the treatment of chronic lymphocytic leukemia in the United States in October 2009. [27] [28]
Ofatumumab (Arzerra) was then approved in the European Union in June 2010, [13] in the United Kingdom in April 2010, [4] and in Canada in August 2012. [29] [30]
In 2014, Novartis acquired a number of GSK's oncology products, including the collaboration with Genmab and ofatumumab. [14] [31]
For commercial reasons ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017. [29] [30] It was withdrawn from the European Union in February 2019. [32] [33] Novartis removed it from all of the non-US markets and made it available only for compassionate use in those markets. [34] [35]
Ofatumumab (Kesimpta) was approved for the treatment of relapsing forms of multiple sclerosis in adults in the United States in August 2020. [36] [37] EU approval was subsequently received in March 2021. [10]
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. [38]
Daclizumab is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T-cells.
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, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion. Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza, Rixathon, Ruxience, and Truxima.
Natalizumab, sold under the brand name Tysabri among others, is a medication used to treat multiple sclerosis and Crohn's disease. It is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. It is given by intravenous infusion. The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood–brain barrier.
Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is used for the treatment of adults with highly active forms of relapsing-remitting multiple sclerosis.
Alemtuzumab, sold under the brand names Campath and Lemtrada among others, is a medication used to treat chronic lymphocytic leukemia and multiple sclerosis. In chronic lymphocytic leukemia, it has been used as both a first line and second line treatment. It is given by injection into a vein.
Ocrelizumab, sold under the brand name Ocrevus, is a medication used for the treatment of multiple sclerosis (MS). It is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and is an immunosuppressive drug. Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds.
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 through the subsidiaries Genmab B.V. in Utrecht, The Netherlands, Genmab U.S., Inc. in Princeton, USA, and Genmab K.K. in Tokyo, Japan. Genmab is a dual-listed company with shares traded on both the Copenhagen Stock Exchange in Denmark and the NASDAQ Global Select Market in the US.
Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-CD20 monoclonal antibody used as a treatment for cancer. It was originated by GlycArt Biotechnology AG and developed by Roche.
Moxetumomab pasudotox, sold under the brand name Lumoxiti, is an anti-CD22 immunotoxin medication for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Moxetumomab pasudotox is a CD22-directed cytotoxin and is the first of this type of treatment for adults with HCL. The drug consists of the binding fragment (Fv) of an anti-CD22 antibody fused to a toxin called PE38. This toxin is a 38 kDa fragment of Pseudomonas exotoxin A.
Ublituximab, sold under the brand name Briumvi, is an immunomodulator used for the treatment of multiple sclerosis. It is a CD20-directed cytolytic monoclonal antibody.
Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia. Ibrutinib also binds to C-terminal Src Kinases. These are off-target receptors for the BTK inhibitor. Ibrutinib binds to these receptors and inhibits the kinase from promoting cell differentiation and growth. This leads to many different side effects like left atrial enlargement and atrial fibrillation during the treatment of Chronic Lymphocytic Leukemia.
Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers.
Acalabrutinib, sold under the brand name Calquence, is a medication used to treat various types of non-Hodgkin lymphoma, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic Lymphoma (CLL/SLL). It may be used both in relapsed as well as in treatment-naive settings.
Duvelisib, sold under the brand name Copiktra, is a medication used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma after other treatments have failed. It is taken by mouth. It is a PI3 kinase inhibitor.
Tisagenlecleucel, sold under the brand name Kymriah, is a CAR T cells medication for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer.
Zanubrutinib, sold under the brand name Brukinsa, is an anticancer medication used for the treatment of mantle cell lymphoma (MCL), Waldenström's macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL). Zanubrutinib is classified as a Bruton's tyrosine kinase (BTK) inhibitor. It is given by mouth.
Brexucabtagene autoleucel, sold under the brand name Tecartus, is a cell-based gene therapy medication for the treatment of mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).
Belantamab mafodotin, sold under the brand name Blenrep, is a medication for the treatment of relapsed and refractory multiple myeloma.
Mosunetuzumab, sold under the brand name Lunsumio, is a monoclonal antibody used for the treatment of follicular lymphoma. It bispecifically binds CD20 and CD3 to engage T-cells. It was developed by Genentech.
Epcoritamab, sold under the brand name Epkinly, is a monoclonal antibody anticancer medication used for the treatment of diffuse large B-cell lymphoma. Epcoritamab is a bispecific CD20-directed CD3 T-cell engager. Epcoritamab was co-developed by AbbVie and Genmab.