Identification

Name
Belimumab
Accession Number
DB08879
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Belimumab is an intravenous immunosupressant for the adjunctive treatment of systemic lupus erythematosus (SLE). More specifically, it is a fully human recombinant IgG1λ monoclonal antibody produced from a recombinant NS0 cell line stably transfected with the belimumab heavy chain and light chain genes. It is the first biological treatment approved for the indication of SLE. Concomitant use with live or inactivated vaccines must be avoided. Belimumab was FDA approved on March 9, 2011. Belimumab consists of 2 heavy chains, and 2 light chains of the lambda subclass. Each heavy chain contains 452 amino acid residues and each light chain contains 214 amino acid residues. There are 3 post-translational modifications: a conserved N-linked glycosylation on the CH2 domain at Asn 303 of the heavy chain, the conversion of the N-terminal glutamine residue of the heavy chain into pyroglutamate, and loss of C-terminal lysine residue of the heavy chain.

Protein structure
Db08879
Protein chemical formula
C6358H9904N1728O2010S44
Protein average weight
147000.0 Da
Sequences
Not Available
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BenlystaPowder, for solution120 mgIntravenousGlaxosmithkline Inc2011-08-24Not applicableCanada
BenlystaInjection, powder, lyophilized, for solution400 mg/5mLIntravenousGlaxoSmithKline Manufacturing SpA2011-03-102018-03-12Us
BenlystaInjection, powder, lyophilized, for solution400 mg/5mLIntravenousHuman Genome Sciences, Inc.2011-03-10Not applicableUs
BenlystaInjection, powder, for solution120 mgIntravenousGlaxo Group Limited2011-07-13Not applicableEu
BenlystaSolution200 mgSubcutaneousGlaxosmithkline IncNot applicableNot applicableCanada
BenlystaSolution200 mg/1mLSubcutaneousHuman Genome Sciences, Inc.2017-07-20Not applicableUs
BenlystaPowder, for solution400 mgIntravenousGlaxosmithkline Inc2011-08-24Not applicableCanada
BenlystaInjection, powder, lyophilized, for solution120 mg/1.5mLIntravenousGlaxoSmithKline Manufacturing SpA2011-03-102018-03-12Us
BenlystaInjection, powder, for solution400 mgIntravenousGlaxo Group Limited2011-07-13Not applicableEu
BenlystaInjection, powder, lyophilized, for solution120 mg/1.5mLIntravenousHuman Genome Sciences, Inc.2011-03-10Not applicableUs
Categories
UNII
73B0K5S26A
CAS number
356547-88-1

Pharmacology

Indication

Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus.

Associated Conditions
Pharmacodynamics

By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA.

Mechanism of action

Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response.

TargetActionsOrganism
ATumor necrosis factor ligand superfamily member 13B
neutralizer
Human
Absorption

Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-∞), 10 mg/kg, SLE patients = 3083.

Volume of distribution

Vdss, 10 mg/kg, SLE patients = 5.29 L.

Protein binding
Not Available
Metabolism

Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes.

Route of elimination
Not Available
Half life

Terminal elimination half-life, 10 mg/kg, SLE patients= 19.4 days; Distribution half-life, 10 mg/kg, SLE patients = 1.75 days.

Clearance

Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day.

Toxicity

The most commonly-reported adverse reactions, occurring in ≥5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections.

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

Interactions

Drug Interactions
DrugInteraction
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Belimumab.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Belimumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Belimumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Belimumab.
AbetimusThe risk or severity of adverse effects can be increased when Abetimus is combined with Belimumab.
AbituzumabThe risk or severity of adverse effects can be increased when Belimumab is combined with Abituzumab.
ActeosideThe risk or severity of adverse effects can be increased when Belimumab is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Belimumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Belimumab.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Belimumab.
Food Interactions
Not Available

References

General References
  1. Scott LJ, Burness CB, McCormack PL: Belimumab: a guide to its use in systemic lupus erythematosus. BioDrugs. 2012 Jun 1;26(3):195-9. doi: 10.2165/11209060-000000000-00000. [PubMed:22428610]
External Links
KEGG Drug
D03068
PubChem Substance
347910378
ChEMBL
CHEMBL1789843
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Belimumab
ATC Codes
L04AA26 — Belimumab
AHFS Codes
  • 92:44.00 — Immunosuppressive Agents
FDA label
Download (420 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentSystemic Lupus Erythematosus (SLE)3
1RecruitingTreatmentGraft Versus Host Disease (GVHD)1
1RecruitingTreatmentTransplantation, Kidney1
1, 2Active Not RecruitingTreatmentKidney Transplant Rejection1
2Active Not RecruitingTreatmentNephritis, Lupus1
2Active Not RecruitingTreatmentSjögren's Syndrome1
2Active Not RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
2CompletedTreatmentGlomerulonephritis, Membranous1
2CompletedTreatmentLupus Erythematosus, Systemic1
2CompletedTreatmentMyasthaenia Gravis1
2CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentSclerosis, Progressive Systemic1
2CompletedTreatmentSjögren's Syndrome2
2CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
2CompletedTreatmentTransplantation, Organ1
2RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD) / Emphysema1
2RecruitingTreatmentLupus Erythematosus, Systemic2
2TerminatedTreatmentDesensitization Before Kidney Transplant1
2TerminatedTreatmentRheumatoid Arthritis1
2TerminatedTreatmentSystemic Lupus Erythematosus (SLE)1
2Unknown StatusTreatmentSymptomatic Waldenstroms Macroglobulinaemia1
2WithdrawnNot AvailablePurpura, Thrombocytopaenic, Idiopathic1
2WithdrawnTreatmentGlomerulonephritis, Membranous1
2, 3RecruitingTreatmentMuscle Inflammation1
3Active Not RecruitingTreatmentNephritis, Lupus1
3Active Not RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
3CompletedTreatmentSystemic Lupus Erythematosus (SLE)7
3CompletedTreatmentVasculitis1
3RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
4Active Not RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
4CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
4No Longer AvailableNot AvailableRheumatoid Arthritis1
4Not Yet RecruitingTreatmentLupus Erythematosus / Lupus Erythematosus, Systemic1
4RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
Not AvailableCompletedNot AvailableLupus Erythematosus, Discoid1
Not AvailableCompletedNot AvailableSystemic Lupus Erythematosus (SLE)1
Not AvailableNo Longer AvailableNot AvailableSystemic Lupus Erythematosus (SLE)1
Not AvailableRecruitingNot AvailableSystemic Lupus Erythematosus (SLE)3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous120 mg
Injection, powder, for solutionIntravenous400 mg
Injection, powder, lyophilized, for solutionIntravenous120 mg/1.5mL
Injection, powder, lyophilized, for solutionIntravenous400 mg/5mL
Powder, for solutionIntravenous120 mg
Powder, for solutionIntravenous400 mg
SolutionSubcutaneous200 mg/1mL
SolutionSubcutaneous200 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2266439No2009-06-162016-10-25Canada
CA2407910No2009-06-162021-06-15Canada

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
Neutralizer
General Function
Receptor binding
Specific Function
Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-ce...
Gene Name
TNFSF13B
Uniprot ID
Q9Y275
Uniprot Name
Tumor necrosis factor ligand superfamily member 13B
Molecular Weight
31222.48 Da

Drug created on May 17, 2013 18:41 / Updated on December 18, 2018 05:46