Belimumab

Identification

Summary

Belimumab is a B-lymphocyte stimulator (BLyS)-specific inhibitor used to treat systemic lupus erythematosus and active lupus nephritis as an add-on therapy.

Brand Names
Benlysta
Generic Name
Belimumab
DrugBank Accession Number
DB08879
Background

Belimumab is a fully human recombinant IgG1λ monoclonal antibody that inhibits soluble human B lymphocyte stimulator protein (BLyS, also referred to as BAFF and TNFSF13B), a B cell survival factor.7 BLyS levels are often elevated in immunodeficient and autoimmune disorders, such as systemic lupus erythematosus (SLE).2,8 By binding to BLyS and blocking its interaction with B cell receptors, belimumab inhibits the survival of B cells. It is produced by recombinant DNA technology in a murine cell (NS0) expression system.7

Belimumab was first approved by the FDA on March 9, 2011,2 making it the newest drug to be approved for the treatment of SLE in more than 50 years.5 It is currently used to treat SLE and lupus nephritis.7

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
C6358H9904N1728O2010S44
Protein Average Weight
147000.0 Da (approximate)
Sequences
>Belimumab ight chain
SSELTQDPAVSVALGQTVRVTCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDR
FSGSSSGNTASLTITGAQAEDEADYYCSSRDSSGNHWVFGGGTELTVLGQPKAAPSVTLF
PPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYL
SLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
>Belimumab heavy chain
QVQLQQSGAEVKKPGSSVRVSCKASGGTFNNNAINWVRQAPGQGLEWMGGIIPMFGTAKY
SQNFQGRVAITADESTGTASMELSSLRSEDTAVYYCARSRDLLLFPHHALSPWGRGTMVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHHHHHH
References:
  1. RCSB PDB: 5Y9K; Structure of the belimumab Fab fragment [Link]
Download FASTA Format
Synonyms
  • Belimumab

Pharmacology

Indication

In the US, belimumab is indicated to treat active systemic lupus erythematosus (SLE) and active lupus nephritis in patients aged five years and older who are receiving standard therapy.7 In Europe, belimumab is also used to treat SLE and lupus nephritis but only in adults.8

The efficacy of belimumab has not been evaluated in patients with severe active central nervous system lupus. Use of belimumab is not recommended in this situation.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofActive systemic lupus erythematosus•••••••••••••••••••••
Adjunct therapy in treatment ofActive systemic lupus erythematosus••••••••••••••••••••••••••• •••••••• •• •••••••••••• •••••••
Adjunct therapy in treatment ofLupus nephritis•••••••••••••••••
Adjunct therapy in treatment ofActive lupus nephritis•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Belimumab works to inhibit the actions of autoreactive, pro-inflammatory B cells that cause chronic inflammation and tissue damage.7 In patients with SLE, belimumab significantly reduced levels of circulating B (CD20+) cells.1

Mechanism of action

Systemic lupus erythematosus (SLE) and lupus nephritis, a common and serious manifestation of SLE,6 are autoimmune disorders characterized by the presence of autoreactive B lymphocytes (B cells), which promotes the production of autoantibodies that cause inflammation and progressive and irreversible tissue damage.1,5 One of the key cytokines involved in B cell homeostasis and survival is B lymphocyte stimulator protein (BLyS),1 which is a member of tumour necrosis factor (TNF) superfamily of cytokines.5 While the contribution of BLyS to the pathophysiology of autoimmune diseases is not fully understood, BLyS has been identified as a key therapeutic target for the treatment of SLE as BLyS levels are elevated in patients with SLE along with other autoimmune diseases.2,8

Belimumab is an antibody directed against BLyS: it selectively binds BLyS with high affinity, neutralizes it, and blocks its interaction with B cell receptors - transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA),5 and BLyS receptor 3 (BR3).1,5 Belimumab ultimately inhibits the survival of B cells, promotes apoptosis, and reduces the differentiation and maturation of B cells into immunoglobulin-producing plasma cells.1,5,7

TargetActionsOrganism
ATumor necrosis factor ligand superfamily member 13B
antibody
Humans
Absorption

The absolute bioavailability was 74-82% following single belimumab SC doses in healthy adults.3 Following administration of 10 mg/kg belimumab via intravenous infusion in adults with SLE, the Cmax was 313 mcg/mL and the AUC0-∞ was 3,083 day x mcg/mL. Following subcutaneous administration of 200 mg belimumab once-weekly in adults with SLE, the Cmax was 108 mcg/mL and the AUC0-∞ was 726 day x mcg/mL.7 In healthy Japanese volunteers, the Tmax was 6.5 days after administration of a single subcutaneous dose of 200 mg/mL belimumab.4

Steady-state exposure was reached after approximately 11 weeks of subcutaneous administration in healthy subjects of patients with SLE.8

Volume of distribution

Following administration of 10 mg/kg belimumab via intravenous infusion or 200 mg belimumab once-weekly in adults with SLE, the volume of distribution (Vss) was 5 L.7

Protein binding

There is no information available.

Metabolism

No formal metabolism studies have been conducted. As belimumab is an antibody, it is expected to undergo degradation mediated by proteolytic enzymes to form small peptides and individual amino acids.8

Route of elimination

There is no information available.

Half-life

Following administration of 10 mg/kg belimumab via intravenous infusion in adults with SLE, the distribution and terminal half-lives were 1.8 days and 19.4 days, respectively. Following subcutaneous administration of 200 mg belimumab once-weekly in adults with SLE, the distribution and terminal half-lives were 1.1 days and 18.3 days, respectively.7

Clearance

Following administration of 10 mg/kg belimumab via intravenous infusion in adults with SLE, systemic clearance was 215 mL/day. Following subcutaneous administration of 200 mg belimumab once-weekly in adults with SLE, systemic clearance was 204 mL/day.7

Adverse Effects
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Toxicity

There is no LD50 data available for belimumab.

There is limited experience with overdosage of belimumab. Two doses of up to 20 mg/kg have been given intravenously to humans with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg.7 In the case of inadvertent overdose, patients should be carefully observed and supportive care administered, as appropriate8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Belimumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Belimumab.
AducanumabThe risk or severity of adverse effects can be increased when Belimumab is combined with Aducanumab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BenlystaInjection, powder, for solution120 mgIntravenousGlaxo Smith Kline (Ireland) Limited2016-09-08Not applicableEU flag
BenlystaPowder, for solution400 mg / vialIntravenousGlaxosmithkline Inc2011-08-24Not applicableCanada flag
BenlystaInjection, solution200 mgSubcutaneousGlaxo Smith Kline (Ireland) Limited2020-12-16Not applicableEU flag
BenlystaInjection, powder, lyophilized, for solution120 mg/1.5mLIntravenousGlaxoSmithKline LLC2011-03-10Not applicableUS flag
BenlystaInjection, solution200 mgSubcutaneousGlaxo Smith Kline (Ireland) Limited2020-12-16Not applicableEU flag

Categories

ATC Codes
L04AG04 — Belimumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
73B0K5S26A
CAS number
356547-88-1

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. [Article]
  2. Stohl W, Hilbert DM: The discovery and development of belimumab: the anti-BLyS-lupus connection. Nat Biotechnol. 2012 Jan 9;30(1):69-77. doi: 10.1038/nbt.2076. [Article]
  3. Cai WW, Fiscella M, Chen C, Zhong ZJ, Freimuth WW, Subich DC: Bioavailability, Pharmacokinetics, and Safety of Belimumab Administered Subcutaneously in Healthy Subjects. Clin Pharmacol Drug Dev. 2013 Oct;2(4):349-57. doi: 10.1002/cpdd.54. Epub 2013 Aug 26. [Article]
  4. Shida Y, Takahashi N, Sakamoto T, Ino H, Endo A, Hirama T: The pharmacokinetics and safety profiles of belimumab after single subcutaneous and intravenous doses in healthy Japanese volunteers. J Clin Pharm Ther. 2014 Feb;39(1):97-101. doi: 10.1111/jcpt.12101. Epub 2013 Oct 5. [Article]
  5. Blair HA, Duggan ST: Belimumab: A Review in Systemic Lupus Erythematosus. Drugs. 2018 Mar;78(3):355-366. doi: 10.1007/s40265-018-0872-z. [Article]
  6. Shrestha S, Budhathoki P, Adhikari Y, Marasini A, Bhandari S, Mir WAY, Shrestha DB: Belimumab in Lupus Nephritis: A Systematic Review and Meta-Analysis. Cureus. 2021 Dec 15;13(12):e20440. doi: 10.7759/cureus.20440. eCollection 2021 Dec. [Article]
  7. FDA Approved Drug Products: BENLYSTA (belimumab) for injection, for intravenous or subcutaneous use (July 2022) [Link]
  8. EMA Approved Drug Products: Benlysta (belimumab) Subcutaneous Injection [Link]
  9. FDA Approved Drug Products: BENLYSTA (belimumab) for injection, for intravenous/subcutaneous use [Link]
KEGG Drug
D03068
PubChem Substance
347910378
RxNav
1092437
ChEMBL
CHEMBL1789843
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Belimumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentSystemic Lupus Erythematosus4
4Not Yet RecruitingTreatmentSystemic Lupus Erythematosus1
4RecruitingBasic ScienceSystemic Lupus Erythematosus1
4RecruitingPreventionSystemic Lupus Erythematosus1
4RecruitingTreatmentAcute Lymphocytic Leukemia, Pediatric / Sjögren's Syndrome (SS)1

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
Injection, solutionParenteral; Subcutaneous200 MG
Injection, solutionSubcutaneous200 mg
Powder, for solutionIntravenous120 mg / vial
Powder, for solutionIntravenous400 mg / vial
SolutionSubcutaneous200 mg/1mL
SolutionSubcutaneous200 mg / 1 mL
Injection, solutionIntravenous120 mg
InjectionIntravenous400 mg
Injection, powder, lyophilized, for solutionIntracavernous400 mg
Injection, powder, for solutionIntravenous
Injection, powder, lyophilized, for solutionIntravenous120 mg
Injection, powder, lyophilized, for solutionIntravenous400 mg
SuspensionSubcutaneous20000000 mg
SolutionIntravenous120.000 mg
SolutionSubcutaneous200 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2266439No2009-06-162016-10-25Canada flag
CA2407910No2009-06-162021-06-15Canada flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
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
References
  1. Blair HA, Duggan ST: Belimumab: A Review in Systemic Lupus Erythematosus. Drugs. 2018 Mar;78(3):355-366. doi: 10.1007/s40265-018-0872-z. [Article]
  2. FDA Approved Drug Products: BENLYSTA (belimumab) for injection, for intravenous or subcutaneous use (July 2022) [Link]

Drug created at May 18, 2013 00:41 / Updated at February 14, 2024 00:55