Ofatumumab

    Ofatumumab is a novel, investigational, fully human monoclonal antibody that targets a membrane-proximal (close to the cell surface) small loop epitope (a portion of a molecule to which an antibody binds) on the CD20 molecule of B-cells.  This epitope is different from the binding sites targeted by other CD20 antibodies currently available.  The CD20 molecule is a key target in CLL therapy because it is expressed on most B-cells in CLL patients.

    [td_text_with_title custom_title=”Latest post”]
    Genmab kommentar

    Genmab submits sBLA for Ofatumumab

    Company Announcement sBLA submitted to US FDA for ofatumumab as maintenance therapy in relapsed CLL by Novartis Submission based on data from interim results of Phase III PROLONG study Copenhagen, Denmark; July 22, 2015 — Genmab A/S (OMX: GEN) announced today that a supplemental Biologics License Application (sBLA) has been submitted to the U.S. Food and […]

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    182141

    Rituximab, Obinutuzumab, and Ofatumumab in CLL

    This is a discussion of practioners of the advantages of known regiments in CLL. The basic conclusion is that Rituxiamab is the prevailing standard, with obinutuzumab as a potential newcomer with a diffenriated method of action. Ofatumumab is given more of a chance in a refrac setting.

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    Gilead

    IND filing Zydelig in combo with Arzerra

    Gilead announces submission of a supplemental New Drug Application to use Zydelig® in combination with ofatumumab in previously treated patients with CLL Submission based on data presented at American Society of Clinical Oncology Meeting 2015 Copenhagen, Denmark; June 1, 2015 — Genmab A/S (OMX: GEN) announced today that Gilead has published that it has submitted […]

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    [/td_text_with_title][td_text_with_title custom_title=”From Wikipedia”]
    Ofatumumab
    Monoclonal antibody
    Type Whole antibody
    Source Human
    Target CD20
    Clinical data
    Trade names Arzerra
    AHFS/Drugs.com Monograph
    MedlinePlus a610009
    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
    Biological half-life 14 days
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    UNII
    ChEMBL
    Chemical and physical data
    Formula C6480H10022N1742O2020S44
    Molar mass 146.1 kg/mol
     NYesY (what is this?)  (verify)

    Ofatumumab[1] (trade name Arzerra, also known as HuMax-CD20) is a fully human monoclonal antibody (for the CD20 protein) 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.

    Medical uses

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

    FDA Approval

    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]

    EMA Approval

    EMA approval on the 14th of June 2010[3] and Health Canada approval on the 13th of August 2012.[5]

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

    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.[6]

    Mechanism

    Ofatumumab is a humanised anti-CD20 monoclonal antibody whose epitope is distinct from that of rituximab.[7] The CD20 antigen is expressed on solely B cell lymphocytes.[7] Compared with rituximab, ofatumumab binds more tightly to CD20 with a slower off-rate.[7] It causes cytotoxicity in the cells that express CD20 by means of complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).[7]

    Clinical trials

    Status of clinical trials of ofatumumab conducted by Genmab and GSK, as of late 2010.

    See also

    References

    1. ^ Zhang, Bodi (2009). "Ofatumumab". MAbs. 1 (4): 326–331. PMC 2726602Freely accessible. PMID 20068404. doi:10.4161/mabs.1.4.8895. 
    2. ^ a b c d "ARZERRA (ofatumumab) injection, solution [GlaxoSmithKline LLC]". DailyMed. GlaxoSmithKline LLC. September 2013. Retrieved 24 January 2014. 
    3. ^ a b c "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. Glaxo Group Ltd. 7 March 2013. Retrieved 24 January 2014. 
    4. ^ a b c d "Arzerra (acetate formulation) -Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmithKline UK. 27 November 2013. Retrieved 24 January 2014. 
    5. ^ "Product Information". Health Canada. GlaxoSmithKline Inc. 13 August 2012. 
    6. ^ a b c "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Retrieved 24 January 2014. 
    7. ^ a b c d Lin, TS (2010). "Ofatumumab: a novel monoclonal anti-CD20 antibody" (PDF). Pharmacogenomics and personalized medicine. 3: 51–59. PMC 3513208Freely accessible. PMID 23226042. 
    8. ^ http://clinicaltrials.gov/ct2/show/NCT00394836?term=nct00394836&rank=1
    9. ^ Clinical trial number NCT00611455 for "Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to MTX Therapy" at ClinicalTrials.gov
    10. ^ Clinical trial number NCT00603525 for "Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to TNF-α Antagonist Therapy" at ClinicalTrials.gov
    11. ^ Clinical trial number NCTNCT01014208 for "Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD" at ClinicalTrials.gov
    12. ^ Clinical trial number NCT00349349 for "HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab" at ClinicalTrials.gov
    13. ^ http://clinicaltrials.gov/ct2/show/NCT00811733?term=nct00811733&rank=1
    14. ^ http://clinicaltrials.gov/ct2/show/NCT00640328?term=nct00640328&rank=1
    source: https://en.wikipedia.org/wiki/Ofatumumab[/td_text_with_title]