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10841 details
Primary information
ID10841
Therapeutic IDTh1204
Protein NameOfatumumab
Sequence>Th1204_Ofatumumab EVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPGSSKSTSGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP
Molecular Weight146100
Chemical FormulaC6480H10022N1742O2020S44
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeApproximately 14 days. Range: 2.3 to 61.5 days
DescriptionOfatumumab is a human monoclonal antibody for the CD20 protein. Ofatumumab binds specifically to both the small and large extracellular loops of the CD20 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B- to mature B-lymphocyte) and on B-cell CLL. The Fab domain of ofatumumab binds to the CD20 molecule and the Fc domain mediates immune effector functions to result in B-cell lysis in vitro. Ofatumumab 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. Ofatumumab was also approved by Health Canada on August 13th, 2012.
Indication/DiseaseOfatumumab is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab
PharmacodynamicsIn patients with CLL refractory to fludarabine and alemtuzumab, the median decrease in circulating CD19-positive B cells was 91% (n = 50) with the 8th infusion and 85% (n = 32) with the 12th infusion. The time to recovery of lymphocytes, including CD19-positive B cells, to normal levels has not been determined.
Mechanism of ActionOfatumumab binds specifically to both the small and large extracellular loops of the CD20 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B- to mature B-lymphocyte) and on B-cell CLL. The CD20 molecule is not shed from the cell surface and is not internalized following antibody binding. The Fab domain of ofatumumab binds to the CD20 molecule and the Fc domain mediates immune effector functions to result in B-cell lysis in vitro. Data suggest that possible mechanisms of cell lysis include complement-dependent cytotoxicity and antibody-dependent, cell-mediated cytotoxicity.
ToxicityThere is limited information on overdose of ofatumumab. Ofatumumab may cause B-cell depletion in the fetus when administered in pregnant women.[L12612]
MetabolismLike other monoclonal antibodies, ofatumumab is expected to undergo lysosomal degradation by the reticuloendothelial system and protein catabolism by a target-mediated disposition pathway.[A40006]
AbsorptionIn one study consisting of patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, the Cmax was 94 µg/mL and the Tmax was 7.3 hours following the first infusion of 300 mg ofatumumab.[A193059] Following subcutaneous injection, ofatumumab is thought to be absorbed primarily into the lymphatic system. Subcutaneous dosing of 20 mg every four weeks resulted in a mean AUCtau of 483 µg
In patients with CLL, the mean volume of distribution at steady-state was 5.8 L.[L12612] Repeated subcutaneous dosing with 20 mg of ofatumumab resulted in a steady-state volume of distribution of 5.42 L.[L15581]
ClearanceIn patients with CLL, the mean clearance at steady-state was 11.6 mL/hour.[L12612] In patients administered ofatumumab subcutaneously in repeated 20 mg injections, the steady-state clearance following B-cell depletion was estimated to be 0.34 L/day.[L15581]
CategoriesAntineoplastic and Immunomodulating Agents
Patents NumberUS8337847
Date of Issue25-12-2012
Date of Expiry25-11-2028
Drug InteractionB-lymphocyte antigen CD20
TargetB-lymphocyte antigen CD20
Brand NameArzerra
CompanyGlaxo Smith Kline Llc
Brand DescriptionGlaxo Smith Kline Llc
Prescribed ForARZERRA (ofatumumab) is indicated, in combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate
Chemical NameNA
FormulationSolution
Physical Appearance Liquid
Route of AdministrationIntravenous
Recommended DosageDilute and administer as an intravenous infusion according to the following schedules. Do not administer as an intravenous push or bolus or as a subcutaneous injection. Pre-medicate before each infusion. For Previously Untreated CLL 300 mg on Day 1 followed 1 week later by 1,000 mg on Day 8 (Cycle 1) followed by 1,000 mg on Day 1 of subsequent 28-day cycles for a minimum of 3 cycles until best response or a maximum of 12 cycles. For Extended Treatment in CLL: 300 mg on Day 1, followed by 1,000 mg 1 week later on Day 8, followed by 1,000 mg 7 weeks later and every 8 weeks thereafter for up to a maximum of 2 years. For Refractory CLL: 300 mg initial dose on Day 1, followed 1 week later by 2,000 mg weekly for 7 doses (Infusions 2 through 8), followed 4 weeks later by 2,000 mg every 4 weeks for 4 doses (Infusions 9 through 12).
ContraindicationNA
Side EffectsInfusion Reactions; Hepatitis B Virus Reactivation; Hepatitis B Virus Infection; Progressive Multifocal Leukoencephalopathy; Tumor Lysis Syndrome; Cytopenias.
Useful Link 1Link
Useful Link 2NA
RemarksNA