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
Download FASTA FormatReferences:
- RCSB PDB: 5Y9K; Structure of the belimumab Fab fragment [Link]
- 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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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in treatment of Active systemic lupus erythematosus •••••••••••• ••••••••• Adjunct therapy in treatment of Active systemic lupus erythematosus •••••••••••• ••••• •••••••••• •••••••• •• •••••••••••• ••••••• Adjunct therapy in treatment of Lupus nephritis •••••••••••• ••••• Adjunct therapy in treatment of Active 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
Target Actions Organism ATumor necrosis factor ligand superfamily member 13B antibodyHumans - 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Belimumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Belimumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Belimumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Belimumab. Aducanumab The risk or severity of adverse effects can be increased when Belimumab is combined with Aducanumab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Benlysta Injection, powder, lyophilized, for solution 120 mg/1.5mL Intravenous GlaxoSmithKline LLC 2011-03-10 Not applicable US Benlysta Injection, powder, lyophilized, for solution 400 mg/5mL Intravenous GlaxoSmithKline Manufacturing SpA 2011-03-10 2018-03-12 US Benlysta Solution 200 mg / 1 mL Subcutaneous Glaxosmithkline Inc 2018-05-14 Not applicable Canada Benlysta Powder, for solution 120 mg / vial Intravenous Glaxosmithkline Inc 2011-08-24 Not applicable Canada Benlysta Injection, solution 200 mg Subcutaneous Glaxo Smith Kline (Ireland) Limited 2020-12-16 Not applicable EU
Categories
- ATC Codes
- L04AA26 — Belimumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic and Immunomodulating Agents
- B Lymphocyte Stimulator-directed Antibody Interactions
- B Lymphocyte Stimulator-specific Inhibitor
- Blood Proteins
- Decreased B Lymphocyte Activation
- Globulins
- Immunoglobulins
- Immunologic Factors
- Immunoproteins
- Immunosuppressive Agents
- Proteins
- Selective Immunosuppressants
- Serum Globulins
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: BENLYSTA (belimumab) for injection, for intravenous or subcutaneous use (July 2022) [Link]
- EMA Approved Drug Products: Benlysta (belimumab) Subcutaneous Injection [Link]
- FDA Approved Drug Products: BENLYSTA (belimumab) for injection, for intravenous/subcutaneous use [Link]
- External Links
- KEGG Drug
- D03068
- PubChem Substance
- 347910378
- 1092437
- ChEMBL
- CHEMBL1789843
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Belimumab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Systemic Lupus Erythematosus 4 4 Not Yet Recruiting Treatment Systemic Lupus Erythematosus 1 4 Recruiting Basic Science Systemic Lupus Erythematosus 1 4 Recruiting Prevention Systemic Lupus Erythematosus 1 4 Recruiting Treatment Immunoglobulin G4 Related Sclerosing Disease 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 120 MG Injection, powder, for solution Intravenous 400 MG Injection, powder, lyophilized, for solution Intravenous 120 mg/1.5mL Injection, powder, lyophilized, for solution Intravenous 400 mg/5mL Injection, solution Parenteral; Subcutaneous 200 MG Injection, solution Subcutaneous 200 mg Powder, for solution Intravenous 120 mg / vial Powder, for solution Intravenous 400 mg / vial Solution Subcutaneous 200 mg/1mL Solution Subcutaneous 200 mg / 1 mL Injection, solution Intravenous 120 mg Injection Intravenous 400 mg Injection, powder, lyophilized, for solution Intracavernous 400 mg Injection, powder, for solution Intravenous Injection, powder, lyophilized, for solution Intravenous 120 mg Injection, powder, lyophilized, for solution Intravenous 400 mg Suspension Subcutaneous 20000000 mg Solution Intravenous 120.000 mg Solution Subcutaneous 200 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2266439 No 2009-06-16 2016-10-25 Canada CA2407910 No 2009-06-16 2021-06-15 Canada
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- 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
Drug created at May 18, 2013 00:41 / Updated at February 14, 2024 00:55