Vedolizumab

Identification

Summary

Vedolizumab is an integrin blocker and anti-inflammatory agent used to manage ulcerative colitis and Crohn's disease in adults with inadequate clinical response to immunomodulators.

Brand Names
Entyvio
Generic Name
Vedolizumab
DrugBank Accession Number
DB09033
Background

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.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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
  • Vedolizumab
External IDs
  • LDP 02
  • LDP-02
  • LDP02
  • MLN-0002
  • MLN-02
  • MLN0002
  • MLN02

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.

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
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
Humans
AIntegrin beta-7
antibody
Humans
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.

Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
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).

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 Vedolizumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Vedolizumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Vedolizumab.
AducanumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Aducanumab.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Vedolizumab.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Vedolizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Vedolizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Alirocumab.
AltretamineThe risk or severity of adverse effects can be increased when Altretamine is combined with Vedolizumab.
AmivantamabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Amivantamab.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
No interactions found.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EntyvioInjection, solution108 mgSubcutaneousTakeda Pharma A/S2021-02-10Not applicableEU flag
EntyvioInjection, powder, lyophilized, for solution300 mg/5mLIntravenousTakeda Pharmaceuticals America, Inc.2014-05-20Not applicableUS flag
EntyvioPowder, for solution300 mg / vialIntravenousTakeda2015-04-21Not applicableCanada flag
EntyvioInjection, solution108 mgSubcutaneousTakeda Pharma A/S2021-02-10Not applicableEU flag
EntyvioInjection, solution108 mgSubcutaneousTakeda Pharma A/S2021-02-10Not applicableEU flag
EntyvioSolution108 mg / 0.68 mLSubcutaneousTakeda2020-07-08Not applicableCanada flag
EntyvioInjection, solution108 mgSubcutaneousTakeda Pharma A/S2021-02-10Not applicableEU flag
EntyvioInjection, powder, for solution300 mgIntravenousTakeda Pharma A/S2016-09-08Not applicableEU flag
EntyvioSolution108 mg / 0.68 mLSubcutaneousTakeda2020-11-20Not applicableCanada flag
EntyvioInjection, solution108 mgSubcutaneousTakeda Pharma A/S2021-02-10Not applicableEU flag

Categories

ATC Codes
L04AA33 — Vedolizumab
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
Not Available

Chemical Identifiers

UNII
9RV78Q2002
CAS number
943609-66-3

References

General References
  1. Ardizzone S, Bianchi Porro G: Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
KEGG Drug
D08083
PubChem Substance
347910392
RxNav
1538097
ChEMBL
CHEMBL1743087
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vedolizumab
FDA label
Download (281 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentCrohn's Disease (CD)1
4Active Not RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis1
4CompletedTreatmentCrohn's Disease (CD)1
4CompletedTreatmentCrohn's Disease (CD) / Ulcerative Colitis1
4CompletedTreatmentPouchitis1
4CompletedTreatmentUlcerative Colitis2
4Not Yet RecruitingBasic ScienceInflammatory Bowel Diseases (IBD) / Psoriasis1
4Not Yet RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis1
4Not Yet RecruitingTreatmentUlcerative Colitis1
4RecruitingTreatmentCrohn Disease of Small Intestine1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous
Injection, powder, for solutionIntravenous300 mg
Injection, powder, for solutionIntravenous; Parenteral
Injection, powder, lyophilized, for solutionIntravenous300 mg/5mL
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous108 mg
Powder, for solutionIntravenous300 mg / vial
SolutionSubcutaneous108 mg / 0.68 mL
PowderIntravenous
Injection, powder, lyophilized, for solutionIntravenous
Injection, solution, concentrateIntravenous300 mg/1vial
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US2012151248No2012-05-022032-05-02US flag

Properties

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

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Drug created on February 20, 2015 22:30 / Updated on July 24, 2021 14:58