Ofatumumab

Overview

Ofatumumab is a fully human monoclonal antibody to CD20, 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 under license from Genmab.[1–5] WP

The most common side effects for ofatumumab (Kesimpta) include upper respiratory tract infection, headache, injection-related reactions, neutropenia, and local injection site reactions.[2][4] WP

Uses, dosage and effects

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.[2][3][6][7][8] WP

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.[7][8][9] WP

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.[10–13] WP

Ofatumumab is under investigation as a potential treatment for follicular lymphoma, diffuse large B cell lymphoma and rheumatoid arthritis. WP⚠ Wikipedia itself has flagged this text: citation needed.

Risks and side effects

Adverse effects

Adverse effects of ofatumumab (Kesimpta) by frequency:[7][8] WP

Very common (>10% frequency): WP

• Upper respiratory tract infection WP
• Injection-related reactions (systemic) WP
• Injection-site reactions (local) WP
• Urinary tract infections WP
• Headache WP

Common (1–10% frequency): WP

• Back pain WP
• Blood immunoglobulin M decreased WP
• Oral herpes WP

Adverse effects of ofatumumab (Arzerra) by frequency: Very common (>10% frequency):[4][10][12] WP

• Lower respiratory tract infection, including pneumonia[4][10][12] WP
• Upper respiratory tract infection[4][10][12] WP
• Rash[4][10][12] WP
• Anemia[4][10][12] WP
• Neutropenia[4][10][12] WP
• Dyspneoa[4][10][12] WP
• Cough[4][10][12] WP
• Nausea[4][10][12] WP
• Diarrhoea[4][10][12] WP
• Pyrexia[4][10][12] WP
• Fatigue[4][10][12] WP
• Bronchitis[4][10][12] WP

Common (1–10% frequency):' WP

• Cytopenia WP
• Sepsis WP
• Infusion reaction WP
• Herpes virus infection WP
• Urinary tract infection WP
• Febrile neutropenia WP
• Leucopenia WP
• Thrombocytopenia WP
• Anaphylactoid reactions WP
• Hypersensitivity WP
• Headache WP
• Tachycardia WP
• Hypotension WP
• Hypertension WP
• Bronchospasm WP
• Hypoxia WP
• Chest discomfort WP
• Pharyngolaryngeal pain WP
• Nasal congestion WP
• Small bowel obstruction WP
• Itchiness WP
• Flushing WP
• Back pain WP
• Cytokine release syndrome WP
• Rigors WP
• Chills WP
• Hyperhidrosis WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

Uncommon (0.1-1% frequency): WP

• Agranulocytosis WP
• Bradycardia WP
• Hepatitis B infection and reactivation WP
• Coagulopathy WP
• Red cell aplasia WP
• Lymphopenia WP
• Anaphylactic reactions WP
• Tumour lysis syndrome WP

Rare (<0.1% frequency): WP

• Hepatitis B infection or reactivation WP

Ofatumumab (Arzerra) 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.[6][14] WP

For more information, please refer to the prescribing information or your doctor. WP

Interactions

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.[7][10][14] WP

Pharmacology

Mechanism

Ofatumumab is a fully human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab. 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 (CDC) and antibody-dependent cellular cytotoxicity (ADCC).[15][16][17] WP

History

History

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. It was approved as Arzerra for the treatment of chronic lymphocytic leukemia in the United States in October 2009.[18][19][20] WP

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.[4][12][21][22] WP

In 2014, Novartis acquired a number of GSK's oncology products, including the collaboration with Genmab and ofatumumab.[5][23] WP

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.[21][22][24–27] WP

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.[3][28][29] WP

Legal status

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.[30] WP

Chemistry

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Hauser SL, Bar-Or A, Cohen JA, Comi G, Correale J, Coyle PK, Cross AH, de Seze J, Leppert D, Montalban X, Selmaj K, Wiendl H, Kerloeguen C, Willi R, Li B, Kakarieka A, Tomic D, Goodyear A, Pingili R, Häring DA, Ramanathan K, Merschhemke M, Kappos L. Ofatumumab versus Teriflunomide in Multiple Sclerosis. The New England Journal of Medicine. August 2020. doi:10.1056/nejmoa1917246 · PMID 32757523
2. Journal / agency Kesimpta- ofatumumab injection, solution. 20 August 2020
3. Journal / agency Kesimpta EPAR. 25 January 2021
4. Journal / agency Arzerra: EPAR – Product Information. 7 March 2013
5. Other Genmab To Transfer Ofatumumab From GSK To Novartis
6. Journal / agency Boxed Warning and new recommendations to decrease risk of hepatitis B. 21 June 2019
7. Journal / agency Kesimpta EPAR
8. Journal / agency Prescribing Information Kesimpta
9. Journal / agency Arneth BM. Impact of B cells to the pathophysiology of multiple sclerosis. Journal of Neuroinflammation. June 2019. doi:10.1186/s12974-019-1517-1 · PMID 31238945 · PMC6593488
10. Journal / agency Arzerra- ofatumumab injection, solution. 22 June 2020
11. Journal / agency Arzerra EPAR. 17 September 2018
12. Other Arzerra (acetate formulation) -Summary of Product Characteristics (SPC). 27 November 2013
13. Journal / agency Arzerra (ofatumumab) Information. 3 November 2018
14. Other Arzerra (ofatumumab) dosing, indications, interactions, and more
15. Journal / agency Lin TS. Ofatumumab: a novel monoclonal anti-CD20 antibody. Pharmacogenomics and Personalized Medicine. 2010. doi:10.2147/PGPM.S6840 · PMID 23226042 · PMC3513208
16. Journal / agency Anonymous Referee #2. Interactive comment on "Sensitivity of the Variability of Mineral Aerosol Simulations to Meteorological Forcing Datasets" by Molly B. Smith et al. Atmospheric Chemistry and Physics. 26 September 2016. doi:10.5194/acp-2016-638-rc1
17. Journal / agency Teeling JL, Mackus WJ, Wiegman LJ, van den Brakel JH, Beers SA, French RR, van Meerten T, Ebeling S, Vink T, Slootstra JW, Parren PW, Glennie MJ, van de Winkel JG. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. Journal of Immunology. July 2006. doi:10.4049/jimmunol.177.1.362 · PMID 16785532
18. Other Genmab – Global Agreement for Humax-CD20
19. Journal / agency Drug Approval Package:Arzerra (Ofatumumab) Injection Application: 125326. 21 January 2010
20. Other Arzerra (ofatumumab) FDA Approval History. 26 October 2009
21. Other Arzerra Product information 86740. 25 April 2012
22. Other Arzerra Product information 86741. 25 April 2012
23. Other GSK completes divestment of rights to ofatumumab for auto-immune indications to Novartis
24. Journal / agency Arzerra: Withdrawn application. 17 September 2018
25. Journal / agency Arzerra: Withdrawal of the marketing authorisation in the European Union. 28 February 2019
26. Other Novartis Withdraws Chronic Leukemia Drug Arzerra From Non-U.S. Markets. 30 January 2018
27. Other Novartis to transition use of Arzerra to compassionate use outside US. 22 January 2018
28. Other FDA approves Novartis Kesimpta (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis. 20 August 2020
29. Journal / agency Ofatumumab (Kesimpta) FDA approval letter
30. Other Genmab Announces Plan to Transition Arzerra (ofatumumab) to an Oncology Access Program for Chronic Lymphocytic Leukemia Patients in the U.S. Copenhagen Stock Exchange:GEN. 20 August 2020

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