Ofatumumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | CD20 |
| Clinical data | |
| Trade names | Arzerra |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a610009 |
| License data |
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| Pregnancy category |
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| Routes of administration | IV |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Elimination half-life | 14 days |
| Identifiers | |
| CAS Number | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C6480H10022N1742O2020S44 |
| Molar mass | 146062.27 g·mol−1 |
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Ofatumumab[2] (trade name Arzerra, also known as HuMax-CD20) is a fully human monoclonal antibody to CD20, 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).[3][4][5]
Adverse effects
Adverse effects by frequency:[3][4][5]
Very common (>10% frequency):
- Lower respiratory tract infection, including pneumonia
- Upper respiratory tract infection
- Rash
- Anemia
- Neutropenia
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):
- Agranulocytosis
- Coagulopathy
- Red cell aplasia
- Lymphopenia
- Anaphylactic shock
- Tumour lysis syndrome
Rare (<0.1% frequency):
- Hepatitis B infection or reactivation
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.[5]
Interactions
No formal drug interaction studies have been conducted with ofatumumab.[3] 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]
History
It received EMA approval in June 2010[4] and Health Canada approval on the 13th of August 2012.[8] and 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[3] MHRA approval on the 19th of April 2010,[5]
See also
- Ocrelizumab, a humanized (90%) anti-CD20 antibody
- Rituximab, a chimerical anti-CD20 antibody
References
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ Zhang, Bodi (2009). "Ofatumumab". mAbs. 1 (4): 326–331. doi:10.4161/mabs.1.4.8895. PMC 2726602. PMID 20068404.
- ^ a b c d "ARZERRA (ofatumumab) injection, solution [GlaxoSmithKline LLC]". DailyMed. GlaxoSmithKline LLC. September 2013. Retrieved 24 January 2014.
- ^ a b c "Arzerra : EPAR - Product Information" (PDF). European Medicines Agency. Glaxo Group Ltd. 7 March 2013. Retrieved 24 January 2014.
- ^ a b c d "Arzerra (acetate formulation) -Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmithKline UK. 27 November 2013. Archived from the original on 4 March 2016. Retrieved 24 January 2014.
- ^ a b c "Arzerra (ofatumumab) dosing, indications, interactions, and more". Medscape Reference. WebMD. Retrieved 24 January 2014.
- ^ a b c d Lin, TS (2010). "Ofatumumab: a novel monoclonal anti-CD20 antibody". Pharmacogenomics and Personalized Medicine. 3: 51–59. PMC 3513208. PMID 23226042.
- ^ "Product Information". Health Canada. GlaxoSmithKline Inc. 13 August 2012. Archived from the original on 3 March 2016.
- Coiffier B, Lepretre S, Pedersen LM, et al. (February 2008). "Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study". Blood. 111 (3): 1094–100. doi:10.1182/blood-2007-09-111781. PMID 18003886.
- Zhang B (July 2009). "Ofatumumab". mAbs. 1 (4): 326–31. doi:10.4161/mabs.1.4.8895. PMC 2726602. PMID 20068404.
- ClinicalTrials.gov: HuMax-CD20 search results