Ofatumumab

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.

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, diffuse large B cell lymphoma and rheumatoid arthritis.

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):

• Back pain
• Blood immunoglobulin M decreased
• Oral herpes

Adverse effects of ofatumumab (Arzerra) by frequency:

Very common (10% frequency):

• Lower respiratory tract infection, including pneumonia
• Upper respiratory tract infection
• Rash
• Anemia
• Neutropenia
• Dyspneoa
• Cough
• Nausea
• Diarrhoea
• Pyrexia
• Fatigue
• Bronchitis

'''Common (1–10% frequency):''''

• Cytopenia
• Sepsis
• Infusion reaction
• Herpes virus infection
• Urinary tract infection
• Febrile neutropenia
• Leucopenia
• Thrombocytopenia
• Anaphylactoid reactions
• Hypersensitivity
• Headache
• Tachycardia
• 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
• Anaphylactic reactions
• Tumour lysis syndrome

**Rare (

• Hepatitis B infection or reactivation

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.

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-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).

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.

Ofatumumab (Arzerra) was then approved in the European Union in June 2010,

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

References

1. (29 January 2020). "Ofatumumab (Arzerra) Use During Pregnancy".
2. (19 August 2021). "AusPAR: Ofatumumab".
3. "Summary for ARTG Entry:196945 Arzerra ofatumumab (rmc) 100mg/5mL injection concentrate vial".
4. (3 August 2022). "Health product highlights 2021: Annexes of products approved in 2021".
5. (14 April 2021). "Kesimpta 20 mg solution for injection in pre-filled pen – Patient Information Leaflet (PIL)".
6. (17 September 2018). "Arzerra EPAR".
7. "Kesimpta Product information".
8. (August 2020). "Ofatumumab versus Teriflunomide in Multiple Sclerosis". The New England Journal of Medicine.
9. (20 August 2020). "Kesimpta- ofatumumab injection, solution".
10. (25 January 2021). "Kesimpta EPAR".
11. (7 March 2013). "Arzerra : EPAR – Product Information". European Medicines Agency.
12. "Kesimpta EPAR".
13. "Prescribing Information Kesimpta".
14. (June 2019). "Impact of B cells to the pathophysiology of multiple sclerosis". Journal of Neuroinflammation.
15. (22 June 2020). "Arzerra- ofatumumab injection, solution".
16. (17 September 2018). "Arzerra EPAR".
17. (27 November 2013). "Arzerra (acetate formulation) -Summary of Product Characteristics (SPC)". GlaxoSmithKline UK.
18. (3 November 2018). "Arzerra (ofatumumab) Information".
19. "Kesimpta – Summary of Product Characteristics (SPC)".
20. (21 June 2019). "Boxed Warning and new recommendations to decrease risk of hepatitis B".
21. "Arzerra (ofatumumab) dosing, indications, interactions, and more". WebMD.
22. (2010). "Ofatumumab: a novel monoclonal anti-CD20 antibody". Pharmacogenomics and Personalized Medicine.
23. (26 September 2016). "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.
24. (July 2006). "The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20". Journal of Immunology.
25. "Genmab – Global Agreement for Humax-CD20".
26. (21 January 2010). "Drug Approval Package:Arzerra (Ofatumumab) Injection Application: 125326".
27. (26 October 2009). "Arzerra (ofatumumab) FDA Approval History".
28. (25 April 2012). "Arzerra Product information 86740".
29. (25 April 2012). "Arzerra Product information 86741".
30. "Genmab To Transfer Ofatumumab From GSK To Novartis".
31. "GSK completes divestment of rights to ofatumumab for auto-immune indications to Novartis".
32. (17 September 2018). "Arzerra: Withdrawn application".
33. (28 February 2019). "Arzerra: Withdrawal of the marketing authorisation in the European Union". European Medicines Agency.
34. (30 January 2018). "Novartis Withdraws Chronic Leukemia Drug Arzerra From Non-U.S. Markets".
35. (22 January 2018). "Novartis to transition use of Arzerra to compassionate use outside US".
36. (20 August 2020). "FDA approves Novartis Kesimpta (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis". Novartis.
37. "Ofatumumab (Kesimpta) FDA approval letter".
38. (20 August 2020). "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". Genmab A/S.