Belimumab

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, for solution400 mgIntravenousGlaxo Group Limited2011-07-13Not applicableEu
BenlystaSolution200 mg/mLSubcutaneousHuman Genome Sciences, Inc.2017-07-20Not applicableUs
BenlystaPowder, for solution400 mgIntravenousGlaxosmithkline Inc2011-08-24Not applicableCanada
BenlystaInjection, powder, lyophilized, for solution120 mg/1.5mLIntravenousHuman Genome Sciences, Inc.2011-03-10Not applicableUs
BenlystaInjection, powder, for solution120 mgIntravenousGlaxo Group Limited2011-07-13Not applicableEu
BenlystaInjection, powder, lyophilized, for solution400 mg/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.

Structured Indications
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
DrugInteractionDrug group
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Belimumab.Approved
AbituzumabThe risk or severity of adverse effects can be increased when Abituzumab is combined with Belimumab.Investigational
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Belimumab.Approved
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Belimumab.Investigational
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Belimumab.Approved, Investigational
apolizumabThe risk or severity of adverse effects can be increased when apolizumab is combined with Belimumab.Investigational
AVE9633The risk or severity of adverse effects can be increased when AVE9633 is combined with Belimumab.Investigational
BapineuzumabThe risk or severity of adverse effects can be increased when Bapineuzumab is combined with Belimumab.Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Belimumab.Investigational
BelataceptThe risk or severity of adverse effects can be increased when Belatacept is combined with Belimumab.Approved
BenralizumabThe risk or severity of adverse effects can be increased when Benralizumab is combined with Belimumab.Approved
BevacizumabThe risk or severity of adverse effects can be increased when Bevacizumab is combined with Belimumab.Approved, Investigational
bivatuzumabThe risk or severity of adverse effects can be increased when bivatuzumab is combined with Belimumab.Investigational
BlinatumomabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Belimumab.Approved
BlosozumabThe risk or severity of adverse effects can be increased when Blosozumab is combined with Belimumab.Investigational
BococizumabThe risk or severity of adverse effects can be increased when Bococizumab is combined with Belimumab.Investigational
Brentuximab vedotinThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Belimumab.Approved
CatumaxomabThe risk or severity of adverse effects can be increased when Catumaxomab is combined with Belimumab.Approved, Investigational
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Belimumab.Approved
CetuximabThe risk or severity of adverse effects can be increased when Cetuximab is combined with Belimumab.Approved
ClazakizumabThe risk or severity of adverse effects can be increased when Clazakizumab is combined with Belimumab.Investigational
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Belimumab.Approved
ConcizumabThe risk or severity of adverse effects can be increased when Concizumab is combined with Belimumab.Investigational
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Belimumab.Approved
CyclophosphamideThe risk or severity of adverse effects can be increased when Belimumab is combined with Cyclophosphamide.Approved, Investigational
DacetuzumabThe risk or severity of adverse effects can be increased when Dacetuzumab is combined with Belimumab.Investigational
DaclizumabThe risk or severity of adverse effects can be increased when Daclizumab is combined with Belimumab.Approved, Investigational
DemcizumabThe risk or severity of adverse effects can be increased when Demcizumab is combined with Belimumab.Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Belimumab.Approved
DepatuxizumabThe risk or severity of adverse effects can be increased when Depatuxizumab is combined with Belimumab.Investigational
DinutuximabThe risk or severity of adverse effects can be increased when Dinutuximab is combined with Belimumab.Approved
EculizumabThe risk or severity of adverse effects can be increased when Eculizumab is combined with Belimumab.Approved, Investigational
EdrecolomabThe risk or severity of adverse effects can be increased when Edrecolomab is combined with Belimumab.Experimental, Investigational
ElotuzumabThe risk or severity of adverse effects can be increased when Elotuzumab is combined with Belimumab.Approved
EmibetuzumabThe risk or severity of adverse effects can be increased when Emibetuzumab is combined with Belimumab.Investigational
EpratuzumabThe risk or severity of adverse effects can be increased when Epratuzumab is combined with Belimumab.Investigational
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Belimumab.Approved, Investigational
EtaracizumabThe risk or severity of adverse effects can be increased when Etaracizumab is combined with Belimumab.Investigational
EtrolizumabThe risk or severity of adverse effects can be increased when Etrolizumab is combined with Belimumab.Investigational
FarletuzumabThe risk or severity of adverse effects can be increased when Farletuzumab is combined with Belimumab.Investigational
FingolimodBelimumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FirategrastThe risk or severity of adverse effects can be increased when Firategrast is combined with Belimumab.Investigational
FontolizumabThe risk or severity of adverse effects can be increased when Fontolizumab is combined with Belimumab.Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Belimumab.Investigational
Gemtuzumab ozogamicinThe risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Belimumab.Approved
GevokizumabThe risk or severity of adverse effects can be increased when Gevokizumab is combined with Belimumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Belimumab.Investigational
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Belimumab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Belimumab.Approved, Withdrawn
IdarucizumabThe risk or severity of adverse effects can be increased when Idarucizumab is combined with Belimumab.Approved
InebilizumabThe risk or severity of adverse effects can be increased when Inebilizumab is combined with Belimumab.Investigational
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Belimumab.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Belimumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Belimumab.Investigational
Inotuzumab ozogamicinThe risk or severity of adverse effects can be increased when Inotuzumab ozogamicin is combined with Belimumab.Approved
IpilimumabThe risk or severity of adverse effects can be increased when Ipilimumab is combined with Belimumab.Approved
IxekizumabThe risk or severity of adverse effects can be increased when Ixekizumab is combined with Belimumab.Approved, Investigational
LabetuzumabThe risk or severity of adverse effects can be increased when Labetuzumab is combined with Belimumab.Investigational
LandogrozumabThe risk or severity of adverse effects can be increased when Landogrozumab is combined with Belimumab.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Belimumab is combined with Leflunomide.Approved, Investigational
LigelizumabThe risk or severity of adverse effects can be increased when Ligelizumab is combined with Belimumab.Investigational
MatuzumabThe risk or severity of adverse effects can be increased when Matuzumab is combined with Belimumab.Investigational
MDX-1100The risk or severity of adverse effects can be increased when MDX-1100 is combined with Belimumab.Investigational
MEDI-528The risk or severity of adverse effects can be increased when MEDI-528 is combined with Belimumab.Investigational
MepolizumabThe risk or severity of adverse effects can be increased when Mepolizumab is combined with Belimumab.Approved, Investigational
MilatuzumabThe risk or severity of adverse effects can be increased when Milatuzumab is combined with Belimumab.Investigational
Mirvetuximab SoravtansineThe risk or severity of adverse effects can be increased when Mirvetuximab Soravtansine is combined with Belimumab.Investigational
MogamulizumabThe risk or severity of adverse effects can be increased when Mogamulizumab is combined with Belimumab.Investigational
motavizumabThe risk or severity of adverse effects can be increased when motavizumab is combined with Belimumab.Investigational
MuromonabThe risk or severity of adverse effects can be increased when Muromonab is combined with Belimumab.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Belimumab is combined with Natalizumab.Approved, Investigational
NecitumumabThe risk or severity of adverse effects can be increased when Necitumumab is combined with Belimumab.Approved
nimotuzumabThe risk or severity of adverse effects can be increased when nimotuzumab is combined with Belimumab.Investigational
NivolumabThe risk or severity of adverse effects can be increased when Nivolumab is combined with Belimumab.Approved
ObinutuzumabThe risk or severity of adverse effects can be increased when Obinutuzumab is combined with Belimumab.Approved
OcrelizumabThe risk or severity of adverse effects can be increased when Ocrelizumab is combined with Belimumab.Approved, Investigational
OfatumumabThe risk or severity of adverse effects can be increased when Ofatumumab is combined with Belimumab.Approved
OlokizumabThe risk or severity of adverse effects can be increased when Olokizumab is combined with Belimumab.Investigational
OmalizumabThe risk or severity of adverse effects can be increased when Omalizumab is combined with Belimumab.Approved, Investigational
OtelixizumabThe risk or severity of adverse effects can be increased when Otelixizumab is combined with Belimumab.Investigational
OzanezumabThe risk or severity of adverse effects can be increased when Ozanezumab is combined with Belimumab.Investigational
PalivizumabThe risk or severity of adverse effects can be increased when Palivizumab is combined with Belimumab.Approved, Investigational
PanitumumabThe risk or severity of adverse effects can be increased when Panitumumab is combined with Belimumab.Approved, Investigational
PembrolizumabThe risk or severity of adverse effects can be increased when Pembrolizumab is combined with Belimumab.Approved
PertuzumabThe risk or severity of adverse effects can be increased when Pertuzumab is combined with Belimumab.Approved
PexelizumabThe risk or severity of adverse effects can be increased when Pexelizumab is combined with Belimumab.Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Belimumab.Approved, Investigational
PRO 140The risk or severity of adverse effects can be increased when PRO 140 is combined with Belimumab.Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Belimumab is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Belimumab.Approved
RamucirumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Belimumab.Approved, Investigational
RanibizumabThe risk or severity of adverse effects can be increased when Ranibizumab is combined with Belimumab.Approved
ReslizumabThe risk or severity of adverse effects can be increased when Reslizumab is combined with Belimumab.Approved, Investigational
RI 624The risk or severity of adverse effects can be increased when RI 624 is combined with Belimumab.Investigational
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Belimumab.Investigational
RituximabThe risk or severity of adverse effects can be increased when Rituximab is combined with Belimumab.Approved
RoflumilastRoflumilast may increase the immunosuppressive activities of Belimumab.Approved
RontalizumabThe risk or severity of adverse effects can be increased when Rontalizumab is combined with Belimumab.Investigational
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Belimumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Belimumab.Approved
Sacituzumab govitecanThe risk or severity of adverse effects can be increased when Sacituzumab govitecan is combined with Belimumab.Investigational
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Belimumab.Approved
SAR3419The risk or severity of adverse effects can be increased when SAR3419 is combined with Belimumab.Investigational
SarilumabThe risk or severity of adverse effects can be increased when Sarilumab is combined with Belimumab.Approved
SGN-40The risk or severity of adverse effects can be increased when SGN-40 is combined with Belimumab.Investigational
SibrotuzumabThe risk or severity of adverse effects can be increased when Sibrotuzumab is combined with Belimumab.Investigational
siplizumabThe risk or severity of adverse effects can be increased when siplizumab is combined with Belimumab.Investigational
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Belimumab.Approved
SolanezumabThe risk or severity of adverse effects can be increased when Solanezumab is combined with Belimumab.Investigational
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Belimumab.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Belimumab.Approved, Investigational
TanezumabThe risk or severity of adverse effects can be increased when Tanezumab is combined with Belimumab.Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Belimumab.Investigational
TeplizumabThe risk or severity of adverse effects can be increased when Teplizumab is combined with Belimumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Belimumab.Investigational
TNX-901The risk or severity of adverse effects can be increased when TNX-901 is combined with Belimumab.Investigational
TocilizumabThe risk or severity of adverse effects can be increased when Tocilizumab is combined with Belimumab.Approved
TofacitinibBelimumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TovetumabThe risk or severity of adverse effects can be increased when Tovetumab is combined with Belimumab.Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Belimumab.Approved, Investigational
Trastuzumab emtansineThe risk or severity of adverse effects can be increased when Trastuzumab emtansine is combined with Belimumab.Approved
UstekinumabThe risk or severity of adverse effects can be increased when Ustekinumab is combined with Belimumab.Approved, Investigational
VedolizumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Belimumab.Approved
VeltuzumabThe risk or severity of adverse effects can be increased when Veltuzumab is combined with Belimumab.Investigational
VisilizumabThe risk or severity of adverse effects can be increased when Visilizumab is combined with Belimumab.Investigational
XmAb 2513The risk or severity of adverse effects can be increased when XmAb 2513 is combined with Belimumab.Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Belimumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Belimumab.Approved
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
1Active Not RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentSystemic Lupus Erythematosus (SLE)2
1Not Yet RecruitingTreatmentGraft Versus Host Disease (GVHD)1
1, 2RecruitingTreatmentKidney Transplant Rejection1
2Active Not RecruitingTreatmentNephritis, Lupus1
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
2Not Yet RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD) / Emphysema1
2RecruitingTreatmentLupus Erythematosus, Systemic1
2RecruitingTreatmentSjögren's Syndrome1
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)3
3CompletedTreatmentSystemic Lupus Erythematosus (SLE)5
3CompletedTreatmentVasculitis1
3Not Yet RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
4Active Not RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
4CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
4No Longer AvailableNot AvailableRheumatoid Arthritis1
4RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
Not AvailableAvailableNot AvailableSystemic Lupus Erythematosus (SLE)1
Not AvailableCompletedNot AvailableLupus Erythematosus, Discoid1
Not AvailableCompletedNot AvailableSystemic Lupus Erythematosus (SLE)1
Not AvailableRecruitingNot AvailableSystemic Lupus Erythematosus (SLE)2

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/mL
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 November 19, 2017 20:34