Identification

Name
Vedolizumab
Accession Number
DB09033  (DB05802)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Vedolizumab is a recombinant humanized IgG1 monoclonal antibody directed against the human lymphocyte α4β7 integrin, a key mediator of gastrointestinal inflammation. It is used in the treatment of moderate to severe active ulcerative colitis and Crohn's disease for patients who have had an inadequate response with, lost response to, or were intolerant to inhibitors of tumor necrosis factor-alpha (TNF-alpha) or other conventional therapies. By blocking its primary target, α4β7 integrin, vedolizumab reduces inflammation in the gut. Vedolizumab is administered by IV infusion over a period of 30 minutes; after the first dose, it is given again at two and six weeks and then every 8 weeks thereafter.

Protein structure
Db09033
Protein chemical formula
C6528H10072N1732O2042S42
Protein average weight
146837.0 Da
Sequences
>Heavy Chain Sequence
QVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYWMHWVRQAPGQRLEWIGEIDPSESNTNY
NQKFKGRVTLTVDISASTAYMELSSLRSEDTAVYYCARGGYDGWDYAIDYWGQGTLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAG
APSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light Chain Sequence
DVVMTQSPLSLPVTPGEPASISCRSSQSLAKSYGNTYLSWYLQKPGQSPQLLIYGISNRF
SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCLQGTHQPYTFGQGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Not Available
External IDs
LDP 02 / LDP-02 / LDP02 / MLN-0002 / MLN-02 / MLN0002 / MLN02 / UNII-9RV78Q2002
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EntyvioInjection, powder, lyophilized, for solution300 mg/5mLIntravenousTakeda2014-05-20Not applicableUs
EntyvioPowder, for solution300 mgIntravenousTakeda2015-04-21Not applicableCanada
EntyvioInjection, powder, for solution300 mgIntravenousTakeda Pharma A/S2014-05-22Not applicableEu
Categories
UNII
9RV78Q2002
CAS number
943609-66-3

Pharmacology

Indication

Vedolizumab is indicated for adult patients with moderately to severely active UC or CD who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids.

Structured Indications
Pharmacodynamics

Non-clinical studies have shown that the pharmacodynamic effects of vedolizumab are reversible upon removal of the antibody: pharmacologic activity of cells inhibited by vedolizumab could be partially restored within 24 hours after removal, with near complete restoration within 4 days. There are no known drug interactions as vedolizumab is a humanized antibody and does not modulate production of cytokines, which is known to affect drug metabolism.

Mechanism of action

Vedolizumab binds to α4β7 integrin, a key mediator of gastrointestinal inflammation expressed on the surfaces of T and B lymphocytes. By selectively inhibiting the α4β7 integrin, vedolizumab inhibits adhesion of lymphocytes to its natural ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thereby preventing lymphocytic cells from entering the gut lamina propria and gut-associated lymphoid tissue (GALT). Specifically inhibiting this pathway alleviates GI inflammation without impairing systemic immune responses.

TargetActionsOrganism
AIntegrin alpha-4
antibody
Human
AIntegrin beta-7
antibody
Human
Absorption

The intended route of administration is intravenous, therefore there is no absorption data and bioavailability is expected to be 100%.

Volume of distribution

Serum apparent volume of distribution at steady-state has been found to be moderately greater than the serum volume. It is therefore expected to be confined to the systemic circulation, as expected for a high molecular weight protein.

Protein binding

Vedolizumab binds specifically to α4β7 integrin but does not bind to, or inhibit function of, α4β1 or αEβ7 integrins. Inhibition of the α4β7 integrin is a shared mechanism with natalizumab, however vedolizumab binds solely to the α4β7 but not the α4β1 integrin, unlike natalizumab which binds to both. As a result, natalizumab modulates the systemic immune system and is associated with other side effects such as progressive multifocal leukoencephalopathy (PML).

Metabolism

The expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.

Route of elimination

Renal clearance is negligible as vedolizumab is a high molecular weight protein.

Half life

Vedolizumab has a long terminal elimination half life of 336 to 362 hr.

Clearance

Vedolizumab has a low clearance of 0.180 to 0.266 ml/hr/kg.

Toxicity

Long-term studies in animals have not been performed to evaluate the carcinogenic potential, mutagenicity, or possible impairments to fertility. Elevated transaminase levels with or without elevated bilirubin has occurred in patients who have received this drug. Progressive multifocal leukoencephalopathy (PML) has not been reported with use of this drug, however it has occurred in patients who have received different integrin receptor antagonists and is therefore considered a risk for this product. Use of vedolizumab may increase risk of developing infections, and one study found that nasopharyngitis occurs more frequently with vedolizumab than with placebo for CD patients (Wang et al, 2014).

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AdalimumabThe risk or severity of infection can be increased when Adalimumab is combined with Vedolizumab.Approved
AfelimomabThe risk or severity of infection can be increased when Afelimomab is combined with Vedolizumab.Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Vedolizumab.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Belimumab.Approved
Certolizumab pegolThe risk or severity of infection can be increased when Certolizumab pegol is combined with Vedolizumab.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Vedolizumab.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Vedolizumab.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Vedolizumab.Approved
EtanerceptThe risk or severity of infection can be increased when Etanercept is combined with Vedolizumab.Approved, Investigational
FingolimodVedolizumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Vedolizumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Vedolizumab.Investigational
GolimumabThe risk or severity of infection can be increased when Golimumab is combined with Vedolizumab.Approved
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Vedolizumab.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Vedolizumab.Approved, Withdrawn
InfliximabThe risk or severity of infection can be increased when Infliximab is combined with Vedolizumab.Approved
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Vedolizumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Vedolizumab.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Vedolizumab.Approved, Investigational
PirfenidoneThe risk or severity of infection can be increased when Pirfenidone is combined with Vedolizumab.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Vedolizumab.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Vedolizumab.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Vedolizumab.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Vedolizumab.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Vedolizumab.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Vedolizumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Vedolizumab.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Vedolizumab.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vedolizumab.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Vedolizumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Vedolizumab.Investigational
TofacitinibVedolizumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Vedolizumab.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Vedolizumab.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Vedolizumab.Approved
Food Interactions
Not Available

References

General References
  1. Ardizzone S, Bianchi Porro G: Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86. [PubMed:16266194]
  2. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [PubMed:19509315]
  3. Krupka N, Baumgart DC: Designing biologic selectivity for inflammatory bowel disease--role of vedolizumab. Drug Des Devel Ther. 2014 Dec 17;9:147-54. doi: 10.2147/DDDT.S50348. eCollection 2015. [PubMed:25552903]
  4. Wang MC, Zhang LY, Han W, Shao Y, Chen M, Ni R, Wang GN, Wei FX, Zhang YW, Xu XD, Zhang YC: PRISMA--efficacy and safety of vedolizumab for inflammatory bowel diseases: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2014 Dec;93(28):e326. doi: 10.1097/MD.0000000000000326. [PubMed:25526490]
External Links
KEGG Drug
D08083
PubChem Substance
347910392
ChEMBL
CHEMBL1743087
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vedolizumab
ATC Codes
L04AA33 — Vedolizumab
AHFS Codes
  • 92:44.00 — Immunosuppressive Agents
FDA label
Download (281 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentCrohn's Disease (CD)1
0Not Yet RecruitingTreatmentDietary Modifications / Ulcerative Colitis (UC)1
1CompletedPreventionInflammatory Bowel Diseases (IBD)1
1CompletedTreatmentHealthy Volunteers1
1Not Yet RecruitingOtherCrohn's Disease (CD) / Ulcerative Colitis (UC)1
1RecruitingOtherMelanoma1
1RecruitingTreatmentAllogeneic peripheral haematopoietic stem cell transplant1
1RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
2CompletedTreatmentCrohn's Disease (CD)1
2CompletedTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
2CompletedTreatmentUlcerative Colitis (UC)1
2Not Yet RecruitingTreatmentCrohn's Disease (CD)1
2Not Yet RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
2Not Yet RecruitingTreatmentGluten Enteropathy1
2Not Yet RecruitingTreatmentHIV-infection/Aids1
2RecruitingTreatmentAllogeneic peripheral haematopoietic stem cell transplant1
2RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
2WithdrawnTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
3Active Not RecruitingOtherCrohn's Disease (CD) / Ulcerative Colitis (UC)1
3Active Not RecruitingTreatmentCrohn's Disease (CD)2
3Active Not RecruitingTreatmentUlcerative Colitis (UC)3
3CompletedTreatmentCrohn's Disease (CD)2
3CompletedTreatmentUlcerative Colitis (UC)1
3Not Yet RecruitingTreatmentCrohn's Disease (CD)1
3Not Yet RecruitingTreatmentUlcerative Colitis (UC)1
3RecruitingTreatmentCrohn's Disease (CD)1
3RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
3WithdrawnTreatmentInflammatory Bowel Diseases (IBD) / Primary Sclerosing Cholangitis (PSC)1
4Not Yet RecruitingTreatmentCrohn Disease of Small Intestine1
4Not Yet RecruitingTreatmentCrohn's Disease (CD)2
4Not Yet RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
4RecruitingTreatmentCrohn's Disease (CD)4
4RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)2
4RecruitingTreatmentUlcerative Colitis (UC)3
Not AvailableNot Yet RecruitingNot AvailableInflammatory Bowel Diseases (IBD)1
Not AvailableNot Yet RecruitingTreatmentUlcerative Colitis (UC)1
Not AvailableRecruitingNot AvailableCrohn's Disease (CD) / Ulcerative Colitis (UC)1
Not AvailableRecruitingNot AvailableCrohn's Disease (CD) / Ulcerative Colitis (UC) / Ulcerative Colitis and Crohn's Disease1
Not AvailableRecruitingDiagnosticInflammatory Bowel Diseases (IBD)1
Not AvailableRecruitingTreatmentCrohn's Disease (CD) / Inflammatory Bowel Diseases (IBD) / Ulcerative Colitis (UC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous300 mg
Injection, powder, lyophilized, for solutionIntravenous300 mg/5mL
Powder, for solutionIntravenous300 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2012151248No2012-05-022032-05-02Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
isoelectric point7.6European Medicines Agency Assessment Report (Procedure No.: EMEA/H/C/002782/0000)

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
Antibody
General Function
Metal ion binding
Specific Function
Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are...
Gene Name
ITGA4
Uniprot ID
P13612
Uniprot Name
Integrin alpha-4
Molecular Weight
114898.745 Da
References
  1. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [PubMed:19509315]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antibody
General Function
Virus receptor activity
Specific Function
Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alph...
Gene Name
ITGB7
Uniprot ID
P26010
Uniprot Name
Integrin beta-7
Molecular Weight
86902.415 Da
References
  1. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [PubMed:19509315]

Drug created on February 20, 2015 15:30 / Updated on November 19, 2017 20:34