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Ofatumumab

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Ofatumumab
Fragment antigen-binding of ofatumumab (PDB: 3GIZ​)
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetCD20
Clinical data
Trade namesArzerra, Kesimpta
Other namesHuMax-CD20, OMB157
AHFS/Drugs.comMonograph
MedlinePlusa621060.html a610009, a621060
License data
Pregnancy
category
Routes of
administration		Intravenous (Arzerra), subcutaneous (Kesimpta)
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life14 days
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6480H10022N1742O2020S44
Molar mass146062.27 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion.[11] Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the EU 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.[12]

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.[12]

It is sold by Novartis under license from Genmab.

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.[8][10][13] The recommended dose is 20 mg of ofatumumab administered by subcutaneous injection with monthly dosing following loading.[14][15]

Treatment with ofatumumab has been shown to rapidly deplete B-cells[14][15] which aids MS pathogenesis by influencing and regulating different autoimmune process such as T-cell production and APC activity.[16] 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][17][5][18] 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.[18]

Ofatumumab is under investigation as a potential treatment for follicular lymphoma, diffuse large B cell lymphoma and rheumatoid arthritis.[citation needed]

Adverse effects

Adverse effects of ofatumumab (Kesimpta) by frequency:[19][15]

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:[7][12][5]
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):'

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.[13][20] Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.[20]

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

Interactions

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.[20] 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.[19]

Mechanism

Ofatumumab is a fully human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[21] Ofatumumab binds to a distinct epitope on small and large extracellular loops of CD20.[22][23] The CD20 antigen is expressed on solely B cell lymphocytes.[21] Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate.[21] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).[21]

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.[24] It was approved as Arzerra for the treatment of chronic lymphocytic leukemia in the United States in October 2009.[25][26]

Ofatumumab (Arzerra) was then approved in the European Union in June 2010[12], in the UK in April 2010[5] and in Canada in August 2012.[27][28]

In 2014 Novartis acquired a number of GSK’s oncology products, including the collaboration with Genmab and ofatumumab.[29][30]

For commercial reasons Ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017.[27][28] It was withdrawn from the European Union in February 2019.[31][32] Novartis removed it from all of the non-US markets and made it available only for compassionate use in those markets.[33][34]

Ofatumumab (Kesimpta) was approved for the treatment of relapsing forms of multiple sclerosis in adults in the United States in August 2020.[35][36] EU approval was subsequently received in March 2021.[10]

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.[37]

References

  1. ^ "Ofatumumab (Arzerra) Use During Pregnancy". Drugs.com. 29 January 2020. Retrieved 22 August 2020.
  2. ^ a b "AusPAR: Ofatumumab". Therapeutic Goods Administration (TGA). 19 August 2021. Retrieved 10 September 2021.
  3. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  4. ^ "Summary for ARTG Entry:196945 Arzerra ofatumumab (rmc) 100mg/5mL injection concentrate vial". Therapeutic Goods Administration (TGA). Retrieved 23 August 2020.
  5. ^ a b c d "Arzerra (acetate formulation) -Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmithKline UK. 27 November 2013. Archived from the original on 4 March 2016. Retrieved 24 January 2014.
  6. ^ "Kesimpta 20 mg solution for injection in pre-filled pen - Patient Information Leaflet (PIL)". (emc). 14 April 2021. Retrieved 16 April 2021.
  7. ^ a b c d "Arzerra- ofatumumab injection, solution". DailyMed. 22 June 2020. Retrieved 21 August 2020.
  8. ^ a b c d "Kesimpta- ofatumumab injection, solution". DailyMed. 20 August 2020. Retrieved 23 August 2020.
  9. ^ "Arzerra EPAR". European Medicines Agency (EMA). Retrieved 21 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. ^ a b c d "Kesimpta EPAR". European Medicines Agency (EMA). 25 January 2021. Retrieved 16 April 2021.
  11. ^ Hauser, Stephen L.; Bar-Or, Amit; Cohen, Jeffrey A.; Comi, Giancarlo; Correale, Jorge; Coyle, Patricia K.; Cross, Anne H.; de Seze, Jerome; Leppert, David; Montalban, Xavier; Selmaj, Krzysztof; Wiendl, Heinz; Kerloeguen, Cecile; Willi, Roman; Li, Bingbing (2020-08-06). "Ofatumumab versus Teriflunomide in Multiple Sclerosis". New England Journal of Medicine. 383 (6): 546–557. doi:10.1056/nejmoa1917246. ISSN 0028-4793.
  12. ^ a b c d "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. 7 March 2013. Retrieved 24 January 2014.
  13. ^ a b "Boxed Warning and new recommendations to decrease risk of hepatitis B". U.S. Food and Drug Administration. 21 June 2019. Retrieved 11 September 2021.
  14. ^ a b "Kesimpta EPAR" (PDF). European Medicines Agency (EMA). Retrieved 31 October 2022.
  15. ^ a b c "Prescribing Information Kesimpta" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 31 October 2022.
  16. ^ Arneth, Borros M. (2019-06-25). "Impact of B cells to the pathophysiology of multiple sclerosis". Journal of Neuroinflammation. 16 (1). doi:10.1186/s12974-019-1517-1. ISSN 1742-2094.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ "Arzerra EPAR". European Medicines Agency (EMA). Retrieved 31 October 2022.
  18. ^ a b "Arzerra (ofatumumab) Information". U.S. Food and Drug Administration (FDA). Retrieved 31 October 2022.
  19. ^ a b "Kesimpta - Summary of Product Characteristics (SPC)" (PDF). European Medicines Agency (EMA). Retrieved 31 October 2022.
  20. ^ a b c "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Retrieved 24 January 2014.
  21. ^ a b c d Lin TS (2010). "Ofatumumab: a novel monoclonal anti-CD20 antibody". Pharmacogenomics and Personalized Medicine. 3: 51–9. doi:10.2147/PGPM.S6840. PMC 3513208. PMID 23226042.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ "Review of Smith et al". 2016-09-26. doi:10.5194/acp-2016-638-rc1. {{cite journal}}: Cite journal requires |journal= (help)CS1 maint: unflagged free DOI (link)
  23. ^ Teeling, Jessica L.; Mackus, Wendy J. M.; Wiegman, Luus J. J. M.; van den Brakel, Jeroen H. N.; Beers, Stephen A.; French, Ruth R.; van Meerten, Tom; Ebeling, Saskia; Vink, Tom; Slootstra, Jerry W.; Parren, Paul W. H. I.; Glennie, Martin J.; van de Winkel, Jan G. J. (2006-07-01). "The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20". The Journal of Immunology. 177 (1): 362–371. doi:10.4049/jimmunol.177.1.362. ISSN 0022-1767.
  24. ^ "Genmab - Global Agreement for Humax-CD20". Genmab - Global Agreement for Humax-CD20. Retrieved 31 October 2022.
  25. ^ "Drug Approval Package:Arzerra (Ofatumumab) Injection Application: 125326". U.S. Food and Drug Administration (FDA). 21 January 2010. Retrieved 21 August 2020. {{cite web}}: Unknown parameter |lay-url= ignored (help)
  26. ^ "Arzerra (ofatumumab) FDA Approval History". Drugs.com. 26 October 2009. Retrieved 21 August 2020.
  27. ^ a b "Arzerra Product information 86740". Drug Product Database. 25 April 2012. Retrieved 21 August 2020.
  28. ^ a b "Arzerra Product information 86741". Drug Product Database. 25 April 2012. Retrieved 21 August 2020.
  29. ^ "Genmab To Transfer Ofatumumab From GSK To Novartis". www.bioprocessonline.com. Retrieved 2022-10-31.
  30. ^ "GSK completes divestment of rights to ofatumumab for auto-immune indications to Novartis | GSK". www.gsk.com. Retrieved 2022-10-31.
  31. ^ "Arzerra: Withdrawn application". European Medicines Agency (EMA). Retrieved 21 August 2020.
  32. ^ "Arzerra: Withdrawal of the marketing authorisation in the European Union" (PDF). European Medicines Agency. 28 February 2019.
  33. ^ "Novartis Withdraws Chronic Leukemia Drug Arzerra From Non-U.S. Markets". FDANews. 30 January 2018. Retrieved 21 August 2020.
  34. ^ "Novartis to transition use of Arzerra to compassionate use outside US". EPM Magazine. 22 January 2018. Retrieved 21 August 2020.
  35. ^ "FDA approves Novartis Kesimpta (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis" (Press release). Novartis. 20 August 2020. Retrieved 21 August 2020.
  36. ^ "Ofatumumab (Kesimpta) FDA approval letter" (PDF).
  37. ^ "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" (Press release). Genmab A/S. 20 August 2020. Retrieved 16 April 2021 – via GlobeNewswire.

Further reading

  • "Ofatumumab". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT01848145 for "Rapid Infusion of Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia" at ClinicalTrials.gov
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