Identification

Name
Ofatumumab
Accession Number
DB06650
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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.

Protein structure
Db06650
Protein chemical formula
C6480H10022N1742O2020S44
Protein average weight
146100.0 Da
Sequences
>Ofatumumab Heavy Chain
EVQLVESGGGLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSTISWNSGSIGY
ADSVKGRFTISRDNAKKSLYLQMNSLRAEDTALYYCAKDIQYGNYYYGMDVWGQGTTVTV
SSASTKGPSVFPLAPGSSKSTSGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP
>Ofatumumab Light Chain
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPITFGQGTRLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNR
Download FASTA Format
Synonyms
  • HuMax-CD20
  • Ofatumumab
  • Ofatumumabum
External IDs
2F2 / GSK-1841157 / HuMax-CD20 / UNII-M95KG522R0
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArzerraInjection, solution20 mg/1mLIntravenousGlaxosmithkline Inc2011-07-222017-08-31Us
ArzerraSolution100 mgIntravenousNovartis2012-08-13Not applicableCanada
ArzerraInjection, solution20 mg/1mLIntravenousNovartis Pharmaceuticals Corporation2016-02-01Not applicableUs
ArzerraInjection20 mg/1mLIntravenousGlaxosmithkline Inc2009-10-262012-03-31Us
ArzerraInjection, solution20 mg/1mLIntravenousNovartis Pharmaceuticals Corporation2016-02-01Not applicableUs
ArzerraSolution1000 mgIntravenousNovartis2012-08-13Not applicableCanada
Categories
UNII
M95KG522R0
CAS number
679818-59-8

Pharmacology

Indication

Ofatumumab is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.

Associated Conditions
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.

TargetActionsOrganism
AB-lymphocyte antigen CD20
inhibitor
Human
Absorption
Not Available
Volume of distribution

From 1.7 to 5.1 L.

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Ofatumumab is eliminated through both a target-independent route and a B cell-mediated route.

Half life

Approximately 14 days. Range: 2.3 to 61.5 days

Clearance

0.01 L/hr Exhibited large inter-subject variability with CV% greater than 50%.

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Ofatumumab.
AbituzumabThe risk or severity of adverse effects can be increased when Ofatumumab is combined with Abituzumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Ofatumumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Ofatumumab.
AducanumabThe risk or severity of adverse effects can be increased when Ofatumumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Ofatumumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ofatumumab.
AlirocumabThe risk or severity of adverse effects can be increased when Ofatumumab is combined with Alirocumab.
AmatuximabThe risk or severity of adverse effects can be increased when Ofatumumab is combined with Amatuximab.
AMG 108The risk or severity of adverse effects can be increased when AMG 108 is combined with Ofatumumab.
Food Interactions
Not Available

References

General References
  1. Lin TS: Ofatumumab: a novel monoclonal anti-CD20 antibody. Pharmgenomics Pers Med. 2010;3:51-9. Epub 2010 May 10. [PubMed:23226042]
  2. Dorner T, Burmester GR: New approaches of B-cell-directed therapy: beyond rituximab. Curr Opin Rheumatol. 2008 May;20(3):263-8. doi: 10.1097/BOR.0b013e3282f5e08d. [PubMed:18388516]
  3. Glennie MJ, French RR, Cragg MS, Taylor RP: Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol. 2007 Sep;44(16):3823-37. [PubMed:17768100]
  4. Du J, Yang H, Guo Y, Ding J: Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20. Mol Immunol. 2009 Jul;46(11-12):2419-23. doi: 10.1016/j.molimm.2009.04.009. Epub 2009 May 8. [PubMed:19427037]
External Links
KEGG Drug
D09314
PubChem Substance
347910355
ChEMBL
CHEMBL1201836
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ofatumumab
ATC Codes
L01XC10 — Ofatumumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (153 KB)
MSDS
Download (92 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma1
1CompletedOtherChronic Lymphocytic Leukaemia (CLL)1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Follicular Lymphoma (FL) / Leukaemia, Lymphocytic, Chronic and Lymphoma, Follicular1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Indolent Non-Hodgkin's Lymphomas / Mantle Cell Lymphoma (MCL)1
1CompletedTreatmentMalignancies1
1CompletedTreatmentRheumatoid Arthritis1
1TerminatedTreatmentB-cell Non-Hodgkin's Lymphomas / Chronic Lymphocytic Leukaemia (CLL)1
1, 2Active Not RecruitingTreatmentChronic Graft Versus Host Disease1
1, 2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)2
1, 2CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia / Prolymphocyctic Leukemia / Richter's Transformation / Small Lymphocytic Lymphoma (SLL)1
1, 2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leukemia (CLL) - Refractory / Leukemia, Prolymphocytic / Recurrent Small Lymphocytic Lymphoma1
1, 2Unknown StatusTreatmentMantle Cell Lymphoma (MCL)1
1, 2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)1
1, 2WithdrawnTreatmentFollicular Lymphoma (FL)1
2Active Not RecruitingTreatmentAdvanced Cancers / Chronic Lymphocytic Leukaemia (CLL) / Leukemias1
2Active Not RecruitingTreatmentB-cell Lymphoid Leukemia / Young Patients1
2Active Not RecruitingTreatmentCLL (Chronic Lymphocytic Leukemia) / Small Lymphocytic Lymphoma (SLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leucemia / Chronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / SLL1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)2
2Active Not RecruitingTreatmentLeukemias / Malignant Lymphomas1
2Active Not RecruitingTreatmentLymphoma, B-Cell1
2Active Not RecruitingTreatmentMalignant Lymphomas2
2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2Active Not RecruitingTreatmentStage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia1
2Active Not RecruitingTreatmentStage I Mantle Cell Lymphoma / Stage II Contiguous Mantle Cell Lymphoma / Stage II Non-Contiguous Mantle Cell Lymphoma / Stage III Mantle Cell Lymphoma / Stage IV Mantle Cell Lymphoma1
2CompletedTreatmentAnn Arbor Stage III Grade 1 Follicular Lymphoma / Ann Arbor Stage III Grade 2 Follicular Lymphoma / Ann Arbor Stage III Grade 3 Follicular Lymphoma / Ann Arbor Stage IV Grade 1 Follicular Lymphoma / Ann Arbor Stage IV Grade 2 Follicular Lymphoma / Ann Arbor Stage IV Grade 3 Follicular Lymphoma / Grade 3a Follicular Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma1
2CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia / Chronic Lymphocytic Leukaemia (CLL) / Contiguous Stage II Small Lymphocytic Lymphoma / Hematopoietic/Lymphoid Cancer / Noncontiguous Stage II Small Lymphocytic Lymphoma / Stage 0 Chronic Lymphocytic Leukemia / Stage I Chronic Lymphocytic Leukemia / Stage I Small Lymphocytic Lymphoma / Stage II Chronic Lymphocytic Leukemia / Stage II Small Lymphocytic Lymphoma / Stage III Chronic Lymphocytic Leukemia / Stage III Small Lymphocytic Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)9
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Fevers / Hypogammaglobulinemia / Lymphadenopathy / Lymphocytosis / Night Sweats / Paraproteinemia / Small Lymphocytic Lymphoma (SLL) / Thrombocytopenias / Tiredness1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2CompletedTreatmentDisseminated Sclerosis1
2CompletedTreatmentFollicular Lymphoma (FL)2
2CompletedTreatmentFollicular Lymphoma (FL) / Marginal Zone Lymphoma / Small Lymphocytic Lymphoma (SLL)1
2CompletedTreatmentHodgkins Disease (HD)1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)2
2CompletedTreatmentLymphoma, Large-Cell, Diffuse2
2CompletedTreatmentNon Previously Treated CD20+ Diffuse Large B-cell Lymphoma1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)2
2CompletedTreatmentPatients With CLL Refractory (SD, PD or CR/PR < 6 Months) Following no More Than Two Prior Treatment Lines / Patients With CLL Relapsing After an Initial Response (CR, PR ≥ 6 Months) Following no More Than Two Prior Treatment Lines; or1
2CompletedTreatmentRelapsed NLPHL1
2CompletedTreatmentRichter's Syndrome1
2CompletedTreatmentStage III Melanoma / Stage IV Melanoma1
2CompletedTreatmentWaldenström's Macroglobulinemia (WM)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Burkitt Leukemia/Lymphoma / Hematopoietic/Lymphoid Cancer / Lymphoma, Lymphoblastic1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
2RecruitingTreatmentDiffuse Large Cell Lymphoma Relapsed/Refractory1
2RecruitingTreatmentFollicular Lymphoma Grade 3A / Follicular Lymphoma, Grade 1 / Follicular Lymphoma, Grade 21
2RecruitingTreatmentGlomerulonephritis minimal lesion2
2RecruitingTreatmentLeukemia, Lymphoblastic, Chronic1
2RecruitingTreatmentLeukemias2
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentRelapsing Multiple Sclerosis (RMS)1
2SuspendedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL)1
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2TerminatedTreatmentLeukemias / Lymphoma, Lymphoblastic / Malignant Lymphomas / Precursor-B Acute Lymphoblastic Leukemia1
2TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)2
2TerminatedTreatmentRecurrent Adult Diffuse Large Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma1
2TerminatedTreatmentRheumatoid Arthritis1
2TerminatedTreatmentWaldenström's Macroglobulinemia (WM)1
2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)1
2WithdrawnTreatmentFollicular Lymphoma (FL) / Lymphoma, B-Cell, Marginal Zone / Lymphoma, Intermediate-Grade / Lymphoma, Low-Grade / Non-Hodgkin's Lymphoma (NHL)1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
3Active Not RecruitingTreatmentFollicular Lymphoma (FL)1
3Active Not RecruitingTreatmentRelapsed or Refractory Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
3Active Not RecruitingTreatmentRelapsing Multiple Sclerosis (RMS)1
3CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)4
3CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
3CompletedTreatmentLymphoma, Large-Cell, Diffuse1
3CompletedTreatmentPemphigus1
3Enrolling by InvitationTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
3Not Yet RecruitingTreatmentRelapsing Multiple Sclerosis (RMS)1
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
3RecruitingTreatmentRelapsing Multiple Scelrosis1
3TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3TerminatedTreatmentPemphigus1
3TerminatedTreatmentRheumatoid Arthritis2
4CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
Not AvailableCompletedNot AvailableChronic Lymphocytic Leukaemia (CLL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous20 mg/1mL
Injection, solutionIntravenous20 mg/1mL
SolutionIntravenous100 mg
SolutionIntravenous1000 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8337847No2012-12-252028-11-25Us
US8975282No2015-03-102032-07-28Us

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Mhc class ii protein complex binding
Specific Function
This protein may be involved in the regulation of B-cell activation and proliferation.
Gene Name
MS4A1
Uniprot ID
P11836
Uniprot Name
B-lymphocyte antigen CD20
Molecular Weight
33076.99 Da
References
  1. Dorner T, Burmester GR: New approaches of B-cell-directed therapy: beyond rituximab. Curr Opin Rheumatol. 2008 May;20(3):263-8. doi: 10.1097/BOR.0b013e3282f5e08d. [PubMed:18388516]
  2. Glennie MJ, French RR, Cragg MS, Taylor RP: Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol. 2007 Sep;44(16):3823-37. [PubMed:17768100]
  3. Du J, Yang H, Guo Y, Ding J: Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20. Mol Immunol. 2009 Jul;46(11-12):2419-23. doi: 10.1016/j.molimm.2009.04.009. Epub 2009 May 8. [PubMed:19427037]

Drug created on March 19, 2008 10:44 / Updated on November 21, 2018 07:14