Ofatumumab

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
MedlinePlusa621050
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.[13] 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.[9][11] Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States.[14] It is sold by Novartis under license from Genmab.[15]

The most common side effects for ofatumumab (Kesimpta) include upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions.[9] The most common side effects for ofatumumab (Arzerra) include infusion reactions and neutropenia.[14]

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.[9][11][16] The recommended dose is 20 mg of ofatumumab administered by subcutaneous injection with monthly dosing following loading.[17][18]

Treatment with ofatumumab has been shown to rapidly deplete B-cells[17][18] which aids MS pathogenesis by influencing and regulating different autoimmune process such as T-cell production and APC activity.[19] 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).[8][20][6][21] 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.[21]

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:[22][18]

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:[8][14][6]
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.[16][23] Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.[23]

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

Interactions

No formal drug interaction studies have been conducted with ofatumumab.[8] 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.[23] 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.[22]

Mechanism

Ofatumumab is a fully human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[24] Ofatumumab binds to a distinct epitope on small and large extracellular loops of CD20.[25][26] The CD20 antigen is expressed on solely B cell lymphocytes.[24] Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate.[24] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).[24]

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.[27] It was approved as Arzerra for the treatment of chronic lymphocytic leukemia in the United States in October 2009.[28][29]

Ofatumumab (Arzerra) was then approved in the European Union in June 2010,[14] in the United Kingdom in April 2010,[6] and in Canada in August 2012.[30][31]

In 2014, Novartis acquired a number of GSK's oncology products, including the collaboration with Genmab and ofatumumab.[15][32]

For commercial reasons ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017.[30][31] It was withdrawn from the European Union in February 2019.[33][34] Novartis removed it from all of the non-US markets and made it available only for compassionate use in those markets.[35][36]

Ofatumumab (Kesimpta) was approved for the treatment of relapsing forms of multiple sclerosis in adults in the United States in August 2020.[37][38] EU approval was subsequently received in March 2021.[11]

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.[39]

References

  1. ^ "Ofatumumab (Arzerra) Use During Pregnancy". Drugs.com. 29 January 2020. Archived from the original on 29 November 2020. Retrieved 22 August 2020.
  2. ^ a b "AusPAR: Ofatumumab". Therapeutic Goods Administration (TGA). 19 August 2021. Archived from the original on 11 September 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 October 2023.
  4. ^ "Summary for ARTG Entry:196945 Arzerra ofatumumab (rmc) 100mg/5mL injection concentrate vial". Therapeutic Goods Administration (TGA). Archived from the original on 28 August 2021. Retrieved 23 August 2020.
  5. ^ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada. 3 August 2022. Archived from the original on 25 March 2024. Retrieved 25 March 2024.
  6. ^ 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.
  7. ^ "Kesimpta 20 mg solution for injection in pre-filled pen - Patient Information Leaflet (PIL)". (emc). 14 April 2021. Archived from the original on 16 April 2021. Retrieved 16 April 2021.
  8. ^ a b c d "Arzerra- ofatumumab injection, solution". DailyMed. 22 June 2020. Archived from the original on 14 February 2021. Retrieved 21 August 2020.
  9. ^ a b c d "Kesimpta- ofatumumab injection, solution". DailyMed. 20 August 2020. Archived from the original on 14 February 2021. Retrieved 23 August 2020.
  10. ^ "Arzerra EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 8 August 2020. Retrieved 21 August 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. ^ a b c d "Kesimpta EPAR". European Medicines Agency (EMA). 25 January 2021. Archived from the original on 16 April 2021. Retrieved 16 April 2021.
  12. ^ "Kesimpta Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
  13. ^ Hauser SL, Bar-Or A, Cohen JA, Comi G, Correale J, Coyle PK, et al. (August 2020). "Ofatumumab versus Teriflunomide in Multiple Sclerosis". The New England Journal of Medicine. 383 (6): 546–557. doi:10.1056/nejmoa1917246. hdl:11573/1473907. PMID 32757523. S2CID 221015936.
  14. ^ a b c d "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. 7 March 2013. Archived from the original (PDF) on 4 February 2014. Retrieved 24 January 2014.
  15. ^ a b "Genmab To Transfer Ofatumumab From GSK To Novartis". www.bioprocessonline.com. Archived from the original on 29 September 2022. Retrieved 31 October 2022.
  16. ^ a b "Boxed Warning and new recommendations to decrease risk of hepatitis B". U.S. Food and Drug Administration. 21 June 2019. Archived from the original on 28 April 2020. Retrieved 11 September 2021.
  17. ^ a b "Kesimpta EPAR" (PDF). European Medicines Agency (EMA). Archived (PDF) from the original on 21 October 2022. Retrieved 31 October 2022.
  18. ^ a b c "Prescribing Information Kesimpta" (PDF). U.S. Food and Drug Administration (FDA). Archived (PDF) from the original on 22 April 2022. Retrieved 31 October 2022.
  19. ^ Arneth BM (June 2019). "Impact of B cells to the pathophysiology of multiple sclerosis". Journal of Neuroinflammation. 16 (1): 128. doi:10.1186/s12974-019-1517-1. PMC 6593488. PMID 31238945.
  20. ^ "Arzerra EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 8 August 2020. Retrieved 31 October 2022.
  21. ^ a b "Arzerra (ofatumumab) Information". U.S. Food and Drug Administration (FDA). 3 November 2018. Archived from the original on 31 October 2022. Retrieved 31 October 2022.
  22. ^ a b "Kesimpta - Summary of Product Characteristics (SPC)" (PDF). European Medicines Agency (EMA). Archived (PDF) from the original on 21 October 2022. Retrieved 31 October 2022.
  23. ^ a b c "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Archived from the original on 2 February 2014. Retrieved 24 January 2014.
  24. ^ a b c d Lin TS (2010). "Ofatumumab: a novel monoclonal anti-CD20 antibody". Pharmacogenomics and Personalized Medicine. 3: 51–59. doi:10.2147/PGPM.S6840. PMC 3513208. PMID 23226042.
  25. ^ Anonymous Referee #2 (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. doi:10.5194/acp-2016-638-rc1.
  26. ^ Teeling JL, Mackus WJ, Wiegman LJ, van den Brakel JH, Beers SA, French RR, et al. (July 2006). "The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20". Journal of Immunology. 177 (1): 362–371. doi:10.4049/jimmunol.177.1.362. PMID 16785532. S2CID 24974085.
  27. ^ "Genmab - Global Agreement for Humax-CD20". Genmab - Global Agreement for Humax-CD20. Retrieved 31 October 2022.
  28. ^ "Drug Approval Package:Arzerra (Ofatumumab) Injection Application: 125326". U.S. Food and Drug Administration (FDA). 21 January 2010. Archived from the original on 10 April 2021. Retrieved 21 August 2020.
  29. ^ "Arzerra (ofatumumab) FDA Approval History". Drugs.com. 26 October 2009. Archived from the original on 1 September 2020. Retrieved 21 August 2020.
  30. ^ a b "Arzerra Product information 86740". Drug Product Database. 25 April 2012. Archived from the original on 22 August 2020. Retrieved 21 August 2020.
  31. ^ a b "Arzerra Product information 86741". Drug Product Database. 25 April 2012. Archived from the original on 22 August 2020. Retrieved 21 August 2020.
  32. ^ "GSK completes divestment of rights to ofatumumab for auto-immune indications to Novartis". GSK (Press release). Archived from the original on 7 October 2022. Retrieved 31 October 2022.
  33. ^ "Arzerra: Withdrawn application". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 28 October 2020. Retrieved 21 August 2020.
  34. ^ "Arzerra: Withdrawal of the marketing authorisation in the European Union" (PDF). European Medicines Agency. 28 February 2019. Archived (PDF) from the original on 28 August 2021. Retrieved 21 August 2020.
  35. ^ "Novartis Withdraws Chronic Leukemia Drug Arzerra From Non-U.S. Markets". FDANews. 30 January 2018. Archived from the original on 28 August 2021. Retrieved 21 August 2020.
  36. ^ "Novartis to transition use of Arzerra to compassionate use outside US". EPM Magazine. 22 January 2018. Archived from the original on 28 August 2021. Retrieved 21 August 2020.
  37. ^ "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. Archived from the original on 24 September 2020. Retrieved 21 August 2020.
  38. ^ "Ofatumumab (Kesimpta) FDA approval letter" (PDF). Archived (PDF) from the original on 12 April 2021. Retrieved 22 August 2020.
  39. ^ "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. Archived from the original on 16 April 2021. Retrieved 16 April 2021 – via GlobeNewswire.

Further reading

  • Clinical trial number NCT01848145 for "Rapid Infusion of Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia" at ClinicalTrials.gov