Ofatumumab

From Wikipedia, the free encyclopedia
Ofatumumab
Ofatumumab 3GIZ.png
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
MedlinePlusa610009
License data
Pregnancy
category
Routes of
administration		Intravenous, subcutaneous
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only) [3][2]
  • CA: Schedule I
  • UK: POM (Prescription only) [4][5]
  • US: ℞-only [6][7]
  • EU: Rx-only [8][9]
  • In general: ℞ (Prescription only)
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?)  

Ofatumumab, sold under the brand name Arzerra among others, is a fully human monoclonal antibody to CD20, which appears to inhibit early-stage B lymphocyte activation. It is FDA approved for treating chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab and for the treatment of multiple sclerosis.[10] It has also shown potential in treating follicular lymphoma, diffuse large B cell lymphoma, rheumatoid arthritis. Ofatumumab is the first marketing application for an antibody produced by Genmab, as well as the first human monoclonal antibody which targets the CD20 molecule that will be available for patients with refractory CLL.

The most common side effects for ofatumumab (Arzerra) include infusion reactions and neutropenia.[6] The most common side effects for ofatumumab (Kesimpta) include upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions.[7]

Medical uses[]

Ofatumumab is indicated for the treatment of untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL).[6][8][11][4]

In the United States and the European Union it is also indicated for the treatment of relapsing forms of multiple sclerosis in adults.[7][9][12]

Adverse effects[]

Adverse effects by frequency:[6][11][4]
Very common (>10% frequency):

  • Lower respiratory tract infection, including pneumonia
  • Upper respiratory tract infection
  • Rash
  • Anemia
  • Neutropenia

Common (1-10% frequency):'

  • Sepsis
  • Herpes virus infection
  • Urinary tract infection
  • Febrile neutropenia
  • Leucopenia
  • Thrombocytopenia
  • Anaphylactoid reactions
  • Hypersensitivity
  • Tachycardia
  • Hypotension
  • Hypertension
  • Bronchospasm
  • Hypoxia
  • Dyspnoea (shortness of breath)
  • Chest discomfort
  • Pharyngolaryngeal pain
  • Cough
  • Nasal congestion
  • Small bowel obstruction
  • Diarrhoea
  • Nausea
  • Urticaria (hives)
  • Itchiness
  • Flushing
  • Back pain
  • Cytokine release syndrome
  • Pyrexia (fever)
  • Rigors
  • Chills
  • Hyperhidrosis
  • Fatigue

Uncommon (0.1-1% frequency):

  • Agranulocytosis
  • Coagulopathy
  • Red cell aplasia
  • Lymphopenia
  • Anaphylactic shock
  • Tumour lysis syndrome

Rare (<0.1% frequency):

  • Hepatitis B infection or reactivation

Ofatumumab has received a black box warning regarding the potential for it to cause progressive multifocal leukoencephalopathy and hepatitis B reactivation.[13][14] Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.[14]

Interactions[]

No formal drug interaction studies have been conducted with ofatumumab.[6] 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.[14]

Mechanism[]

Ofatumumab is a human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[15] The CD20 antigen is expressed on solely B cell lymphocytes.[15] Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate.[15] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).[15]

History[]

Ofatumumab was developed by Swiss pharmaceutical company Novartis. As Arzerra it was approved for medical use in the United States in October 2009.[16][17]

Ofatumumab (Arzerra) was approved for medical use in the European Union in June 2010,[11] and for use in Canada in August 2012.[18][19] It was approved for use in the UK in April 2010.[4]

For commercial reasons, Ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017.[18][19] It was withdrawn from the European Union in February 2019.[20][21] Novartis removed it from all of the non-US markets and made it available only for compassionate use in those markets.[22][23]

Ofatumumab (Kesimpta) was approved for medical use in the United States in August 2020.[12][24] On 28 January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kesimpta, intended for the treatment of adults with active relapsing forms of multiple sclerosis.[25] The applicant for this medicinal product is Novartis Ireland Limited.[25] Ofatumumab (Kesimpta) was approved for medical use in the European Union in March 2021.[9]

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.[26]

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. ^ "Summary for ARTG Entry:196945 Arzerra ofatumumab (rmc) 100mg/5mL injection concentrate vial". Therapeutic Goods Administration (TGA). Retrieved 23 August 2020.
  4. ^ 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.
  5. ^ "Kesimpta 20 mg solution for injection in pre-filled pen - Patient Information Leaflet (PIL)". (emc). 14 April 2021. Retrieved 16 April 2021.
  6. ^ a b c d e "Arzerra- ofatumumab injection, solution". DailyMed. 22 June 2020. Retrieved 21 August 2020.
  7. ^ a b c "Kesimpta- ofatumumab injection, solution". DailyMed. 20 August 2020. Retrieved 23 August 2020.
  8. ^ a b "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.
  9. ^ a b c "Kesimpta EPAR". European Medicines Agency (EMA). 25 January 2021. Retrieved 16 April 2021.
  10. ^ "Arzerra (ofatumumab) Information". U.S. Food and Drug Administration. 3 November 2018. Retrieved 11 September 2021.
  11. ^ a b c "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. 7 March 2013. Retrieved 24 January 2014.
  12. ^ a b "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.
  13. ^ "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 c "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Retrieved 24 January 2014.
  15. ^ 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.
  16. ^ "Drug Approval Package:Arzerra (Ofatumumab) Injection Application: 125326". U.S. Food and Drug Administration (FDA). 21 January 2010. Retrieved 21 August 2020. Lay summary (PDF). {{cite web}}: Cite uses deprecated parameter |lay-url= (help)
  17. ^ "Arzerra (ofatumumab) FDA Approval History". Drugs.com. 26 October 2009. Retrieved 21 August 2020.
  18. ^ a b "Arzerra Product information 86740". Drug Product Database. 25 April 2012. Retrieved 21 August 2020.
  19. ^ a b "Arzerra Product information 86741". Drug Product Database. 25 April 2012. Retrieved 21 August 2020.
  20. ^ "Arzerra: Withdrawn application". European Medicines Agency (EMA). Retrieved 21 August 2020.
  21. ^ "Arzerra: Withdrawal of the marketing authorisation in the European Union" (PDF). European Medicines Agency. 28 February 2019.
  22. ^ "Novartis Withdraws Chronic Leukemia Drug Arzerra From Non-U.S. Markets". FDANews. 30 January 2018. Retrieved 21 August 2020.
  23. ^ "Novartis to transition use of Arzerra to compassionate use outside US". EPM Magazine. 22 January 2018. Retrieved 21 August 2020.
  24. ^ "Ofatumumab (Kesimpta) FDA approval letter" (PDF).
  25. ^ a b "Kesimpta: Pending EC decision". European Medicines Agency (EMA). 29 January 2021. Archived from the original on 1 February 2021. Retrieved 1 February 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  26. ^ "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[]

External links[]

  • "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
Retrieved from ""