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| Primary information |
|---|
| ID | 10841 |
| Therapeutic ID | Th1204 |
| Protein Name | Ofatumumab |
| Sequence | >Th1204_Ofatumumab
EVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGYADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPGSSKSTSGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP
|
| Molecular Weight | 146100 |
| Chemical Formula | C6480H10022N1742O2020S44 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Approximately 14 days. Range: 2.3 to 61.5 days |
| Description | Ofatumumab 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/Disease | Ofatumumab is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab |
| Pharmacodynamics | In 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 Action | 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 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. |
| Toxicity | There is limited information on overdose of ofatumumab. Ofatumumab may cause B-cell depletion in the fetus when administered in pregnant women.[L12612] |
| Metabolism | Like other monoclonal antibodies, ofatumumab is expected to undergo lysosomal degradation by the reticuloendothelial system and protein catabolism by a target-mediated disposition pathway.[A40006] |
| Absorption | In 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] |
| Clearance | In 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] |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | US8337847 |
| Date of Issue | 25-12-2012 |
| Date of Expiry | 25-11-2028 |
| Drug Interaction | B-lymphocyte antigen CD20 |
| Target | B-lymphocyte antigen CD20 |
| Brand Name | Arzerra |
| Company | Glaxo Smith Kline Llc |
| Brand Description | Glaxo Smith Kline Llc |
| Prescribed For | ARZERRA (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 Name | NA |
| Formulation | Solution |
| Physical Appearance | Liquid |
| Route of Administration | Intravenous |
| Recommended Dosage | Dilute 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). |
| Contraindication | NA |
| Side Effects | Infusion Reactions; Hepatitis B Virus Reactivation; Hepatitis B Virus Infection; Progressive Multifocal Leukoencephalopathy; Tumor Lysis Syndrome; Cytopenias. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |