Ofatumumab

Ofatumumab
Fragment antigen-binding of ofatumumab (PDB: 3GIZ​)
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetCD20
Names
Trade namesArzerra, Kesimpta
Other namesHuMax-CD20, OMB157
Clinical data
Drug classMonoclonal antibody
Main usesChronic lymphocytic leukemia (CLL), multiple sclerosis[1][2]
Side effectsUpper respiratory tract infection, urinary tract infections, pain at the site of injection, headache, fever, tiredness[3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
    Routes of
    use    		Intravenous, subcutaneous
    External links
    AHFS/Drugs.comGeneral: Monograph
    Systemic: Monograph
    MedlinePlusa610009
    Legal
    License data
    Legal status
    Pharmacokinetics
    Elimination half-life14 days
    Chemical and physical data
    FormulaC6480H10022N1742O2020S44
    Molar mass146062.27 g·mol−1

    Ofatumumab, sold under the brand name Arzerra among others, is a medication used to treat chronic lymphocytic leukemia (CLL) and multiple sclerosis.[1][2] For CLL it is used for cases when fludarabine and alemtuzumab have failed.[1] It is given by injection under the skin or into a vein.[1][2]

    Common side effects include upper respiratory tract infection, urinary tract infections, pain at the site of injection, headache, fever, and tiredness.[3] Other side effects may include reactivation of hepatitis B and progressive multifocal leukoencephalopathy.[1] Risk with breastfeeding is believed to be low.[12] It is a monoclonal antibody that attaches to CD20 on B cells thus decreasing their activity.[3]

    Ofatumumab was approved for medical use in the United States in 2009.[2] While it was approved for CLL in Europe in 2010, this approval was subsequently withdrawn.[13] In 2021 Europe approved its use for MS.[3] In the United Kingdom 20 mg of medication costs the NHS about £1,500.[12] In the United States this amount costs about 7,500 USD.[14]

    Medical uses

    Ofatumumab is indicated for the treatment of untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL).[8][10][15][6]

    In the United States and the European Union it is also indicated for the treatment of relapsing forms of multiple sclerosis in adults.[9][11][16]

    Dosage

    For MS it is given at a dose of 20 mg at time 0, 1 week, and 2 weeks.[2] It is than given every 4 weeks.[2]

    Side effects

    By frequency:[8][15][6]
    Very common (>10% frequency):

    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):

    Rare (<0.1% frequency):

    Ofatumumab has received a black box warning regarding the potential for it to cause progressive multifocal leukoencephalopathy and hepatitis B reactivation.[17] Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.[17]

    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.[17]

    Mechanism

    Ofatumumab is a human anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[18] The CD20 antigen is expressed on solely B cell lymphocytes.[18] Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate.[18] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).[18]

    History

    Ofatumumab (Arzerra) was approved for medical use in the United States in October 2009.[19][20]

    Ofatumumab (Arzerra) was approved for medical use in the European Union in June 2010,[15] and for use in Canada in August 2012.[21][22] It was approved for use in the UK in April 2010.[6]

    For commercial reasons, Ofatumumab (Arzerra) was withdrawn from the Canadian market in 2017.[21][22] It was withdrawn from the European Union in February 2019.[23][24] Novartis removed it from all of the non-US markets and made it available only for compassionate use in those markets.[25][26]

    Ofatumumab (Kesimpta) was approved for medical use in the United States in August 2020.[16][27] 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.[28] The applicant for this medicinal product is Novartis Ireland Limited.[28] Ofatumumab (Kesimpta) was approved for medical use in the European Union 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.[29]

    References

    1. 1 2 3 4 5 "Ofatumumab (Systemic) Monograph for Professionals". Drugs.com. Archived from the original on 21 January 2021. Retrieved 7 November 2021.
    2. 1 2 3 4 5 6 "Ofatumumab Monograph for Professionals". Drugs.com. Archived from the original on 23 May 2020. Retrieved 7 November 2021.
    3. 1 2 3 4 "Kesimpta". Archived from the original on 16 April 2021. Retrieved 7 November 2021.
    4. ↑ "Ofatumumab (Arzerra) Use During Pregnancy". Drugs.com. 29 January 2020. Archived from the original on 29 November 2020. Retrieved 22 August 2020.
    5. ↑ "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.
    6. 1 2 3 4 "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. 1 2 3 4 "Arzerra- ofatumumab injection, solution". DailyMed. 22 June 2020. Archived from the original on 14 February 2021. Retrieved 21 August 2020.
    9. 1 2 "Kesimpta- ofatumumab injection, solution". DailyMed. 20 August 2020. Archived from the original on 14 February 2021. Retrieved 23 August 2020.
    10. 1 2 "Arzerra EPAR". European Medicines Agency (EMA). Archived from the original on 8 August 2020. Retrieved 21 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    11. 1 2 3 "Kesimpta EPAR". European Medicines Agency (EMA). 25 January 2021. Archived from the original on 16 April 2021. Retrieved 16 April 2021.
    12. 1 2 "Ofatumumab". SPS - Specialist Pharmacy Service. 3 February 2016. Archived from the original on 8 November 2021. Retrieved 7 November 2021.
    13. ↑ "Arzerra". Archived from the original on 8 August 2020. Retrieved 7 November 2021.
    14. ↑ "Kesimpta Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 7 November 2021.
    15. 1 2 3 "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. 7 March 2013. Archived (PDF) from the original on 4 February 2014. Retrieved 24 January 2014.
    16. 1 2 "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.
    17. 1 2 3 "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Archived from the original on 2 February 2014. Retrieved 24 January 2014.
    18. 1 2 3 4 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.
    19. ↑ "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.
    20. ↑ "Arzerra (ofatumumab) FDA Approval History". Drugs.com. 26 October 2009. Archived from the original on 1 September 2020. Retrieved 21 August 2020.
    21. 1 2 "Arzerra Product information 86740". Drug Product Database. 25 April 2012. Archived from the original on 22 August 2020. Retrieved 21 August 2020.
    22. 1 2 "Arzerra Product information 86741". Drug Product Database. 25 April 2012. Archived from the original on 22 August 2020. Retrieved 21 August 2020.
    23. ↑ "Arzerra: Withdrawn application". European Medicines Agency (EMA). Archived from the original on 28 October 2020. Retrieved 21 August 2020.
    24. ↑ "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 25 June 2021.
    25. ↑ "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.
    26. ↑ "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.
    27. ↑ "Ofatumumab (Kesimpta) FDA approval letter" (PDF). Archived (PDF) from the original on 2021-04-12. Retrieved 2021-06-25.
    28. 1 2 "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.
    29. ↑ "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.
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