Ofatumumab

Ofatumumab[1] (trade name Arzerra, also known as HuMax-CD20) 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 (Campath) and has also shown potential in treating follicular lymphoma, diffuse large B cell lymphoma, rheumatoid arthritis and relapsing remitting multiple sclerosis. Ofatumumab has also received conditional approval in Europe for the treatment of refractory chronic lymphocytic leukemia. This makes ofatumumab 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.

Ofatumumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetCD20
Clinical data
Trade namesArzerra
AHFS/Drugs.comMonograph
MedlinePlusa610009
License data
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    administration    		IV
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only)
    • US: ℞-only
    Pharmacokinetic data
    Elimination half-life14 days
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    UNII
    ChEMBL
    Chemical and physical data
    FormulaC6480H10022N1742O2020S44
    Molar mass146.1 kg/mol g·mol−1
     NY (what is this?)  (verify)

    Medical uses

    Its only indication that has received regulatory approval is chronic lymphocytic leukemia (CLL).[2][3][4]

    Adverse effects

    Adverse effects by frequency:[2][3][4]
    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.[5] Likewise it is also advised that doctors watch cautiously for small bowel obstruction, neutropenia, thrombocytopenia, infusion reactions or an increased risk for infection.[5]

    Contraindications

    It is contraindicated in individuals that have hypersensitivity to ofatumumab or any of its excipients.[4]

    Interactions

    No formal drug interaction studies have been conducted with ofatumumab.[2] 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.[5]

    Mechanism

    Ofatumumab is a humanised anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[6] The CD20 antigen is expressed on solely B cell lymphocytes.[6] Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate.[6] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).[6]

    History

    It received EMA approval in June 2010[3] and Health Canada approval on the 13th of August 2012.[7] and it first received FDA approval on April 17, 2014, for use in combination with chlorambucil, for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate[2] MHRA approval on the 19th of April 2010,[4]

    See also

    References
    1. Zhang, Bodi (2009). "Ofatumumab". mAbs. 1 (4): 326–331. doi:10.4161/mabs.1.4.8895. PMC 2726602. PMID 20068404.
    2. "ARZERRA (ofatumumab) injection, solution [GlaxoSmithKline LLC]". DailyMed. GlaxoSmithKline LLC. September 2013. Retrieved 24 January 2014.
    3. "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. Glaxo Group Ltd. 7 March 2013. Retrieved 24 January 2014.
    4. "Arzerra (acetate formulation) -Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmithKline UK. 27 November 2013. Retrieved 24 January 2014.
    5. "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Retrieved 24 January 2014.
    6. Lin, TS (2010). "Ofatumumab: a novel monoclonal anti-CD20 antibody". Pharmacogenomics and Personalized Medicine. 3: 51–59. PMC 3513208. PMID 23226042.
    7. "Product Information". Health Canada. GlaxoSmithKline Inc. 13 August 2012. Archived from the original on 3 March 2016.
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