Ofatumumab

Ofatumumab
Ofatumumab ?
Monoclonal antibody
Type Whole antibody
Source Human
Target CD20
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a610009
Licence data US FDA:link
Pregnancy cat.  ?
Legal status ℞-only (US)
Routes Intravenous, subcutaneous
Identifiers
CAS number 679818-59-8 N
ATC code L01XC10
UNII M95KG522R0 YesY
ChEMBL CHEMBL1201836 N
Chemical data
Formula C6480H10022N1742O2020S44 
Mol. mass 146.1 kDa
 N(what is this?)  (verify)

Ofatumumab[1] (trade name Arzerra, also known as HuMax-CD20) is a 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 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.

Contents

Mechanism

Ofatumumab targets an epitope different from rituximab and most other CD20 directed antibodies. Ofatumumab binds to both the small and large loops of the CD20 molecule on B cells. Its location is in closer proximity to the membrane, which in theory allows for more effective complement deposition and subsequent B cell killing. The CD20 molecule is highly expressed in both normal and malignant B cells.

Approvals and indications

It was approved by FDA in Oct 2009 for chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab.[2] It was conditionally approved by the EMA for refractory chronic lymphocytic leukemia in 2010.

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 2726602. PMID 20068404. http://www.landesbioscience.com/journals/17/article/8895/. 
  2. ^ FDA Approves Ofatumumab (Arzerra) for Patients With CLL Refractory to Fludarabine and Alemtuzumab, October 2009
  3. ^ http://clinicaltrials.gov/ct2/show/NCT00394836?term=nct00394836&rank=1
  4. ^ ClinicalTrials.gov NCT00611455 Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to MTX Therapy
  5. ^ ClinicalTrials.gov NCT00603525 Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to TNF-α Antagonist Therapy
  6. ^ ClinicalTrials.gov NCTNCT01014208 Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD
  7. ^ ClinicalTrials.gov NCT00349349 HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab
  8. ^ http://clinicaltrials.gov/ct2/show/NCT00811733?term=nct00811733&rank=1
  9. ^ http://clinicaltrials.gov/ct2/show/NCT00640328?term=nct00640328&rank=1
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#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III


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