Ofatumumab

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
  • US: C (Risk not ruled out)
Routes of
administration		 IV
ATC code L01XC10 (WHO)
Legal status
Legal status
Pharmacokinetic data
Biological half-life 14 days
Identifiers
CAS Number 679818-59-8 N
DrugBank DB06650 N
ChemSpider none
UNII M95KG522R0 YesY
ChEMBL CHEMBL1201836 N
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 non-Hodgkin’s 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 leukaemia (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. doi:10.4161/mabs.1.4.8895. PMC 2726602Freely accessible. PMID 20068404.
  2. 1 2 3 4 "ARZERRA (ofatumumab) injection, solution [GlaxoSmithKline LLC]". DailyMed. GlaxoSmithKline LLC. September 2013. Retrieved 24 January 2014.
  3. 1 2 3 "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. Glaxo Group Ltd. 7 March 2013. Retrieved 24 January 2014.
  4. 1 2 3 4 "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. 1 2 3 "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Retrieved 24 January 2014.
  7. 1 2 3 4 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
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