Vedolizumab

Identification

Summary

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

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 implicated in diseases like ulcerative colitis or Crohn's disease.⁶ α4β7 integrin facilitates the interaction between lymphocytes and gut endothelial cells through the α4β7 integrin-MAdCAM1 interaction, leading to the mobilization of lymphocytes and thus contributing to gastrointestinal inflammation.⁶ Integrins implicated in cell migration into the intestinal tract included α2β2, α4β1, and α4β7; however, the selective activity of vedolizumab against α4β7 integrin has been thought to contribute to its more favorable safety profile compared to its predecessor natalizumab, the first integrin receptor antagonist approved by the FDA.⁵ 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.⁶

Vedolizumab was developed by Takeda and approved by the FDA under the brand name ENTYVIO for the maintenance therapy of moderately to severely active Ulcerative Colitis and Crohn’s Disease in April and September 2023, respectively.^8,9

Type

Biotech

Groups

Approved

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Structure

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 Ulcerative Colitis or Crohn’s disease.⁶

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Associated Conditions

Contraindications & Blackbox Warnings

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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 the production of cytokines, which is known to affect drug metabolism.⁷

The α4β7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the gastrointestinal tract. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is mainly expressed on gut endothelial cells and plays a critical role in homing T-lymphocytes to gut lymph tissue. The interaction of the α4β7 integrin with MAdCAM-1 has been implicated as an important contributor to chronic inflammation, a hallmark of ulcerative colitis and Crohn’s disease. Inhibition of α4β7 integrin by vedolizumab prevents the adhesion of lymphocytes to its natural ligand, thus decreasing the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue.⁶

In clinical trials with vedolizumab at doses ranging from 0.2 to 10 mg/kg (which includes doses outside of the recommended dose), saturation of α4β7 receptors on subsets of circulating lymphocytes involved in gut-immune surveillance was observed.⁶

In clinical trials with vedolizumab at doses ranging from 0.2 to 10 mg/kg and 180 to 750 mg (which include doses outside of the recommended dose) in healthy subjects and in patients with ulcerative colitis or Crohn’s disease, vedolizumab did not elevate neutrophils, basophils, eosinophils, B-helper and cytotoxic T-lymphocytes, total memory helper T-lymphocytes, monocytes or natural killer cells.⁶

A reduction in gastrointestinal inflammation was observed in rectal biopsy specimens from Phase 2 ulcerative colitis patients exposed to vedolizumab for four or six weeks compared to placebo control as assessed by histopathology.⁶

In a study of 14 healthy subjects, vedolizumab did not affect the CD4+ lymphocyte cell counts, CD8+ lymphocyte cell counts, or the CD4+:CD8+ ratios in the CSF.⁶

Mechanism of action

Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin and blocks the interaction of α4β7 integrin with MAdCAM-1. Vedolizumab does not bind to or inhibit the function of the α4β1 and αEβ7 integrins and does not antagonize the interaction of α4 integrins with vascular cell adhesion molecule-1 (VCAM-1).⁶

Target	Actions	Organism
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%. Following the administration of 300 mg of vedolizumab as a 30-minute intravenous infusion from week 0 to 2 and 300 mg every eight weeks starting from Week 6, the trough serum concentration of vedolizumab is 26.3 ± 12.9 and 27.4 ± 19.2 mcg/mL for Ulcerative Colitis and Crohn’s Disease patients respectively at week 6.⁷ At week 46, the trough serum concentration of vedolizumab is 11.2 ± 7.2 and 13.0 ± 9.1 mcg/mL for Ulcerative Colitis and Crohn’s Disease patients respectively.⁷

Volume of distribution

Serum apparent volume of distribution at steady-state has been found to be moderately greater than the serum volume (approximately 5L).^6,7 It is therefore expected to be confined to the systemic circulation, as expected for a high molecular weight protein.⁷

Protein binding

Vedolizumab is a therapeutic monoclonal antibody and is not expected to bind to plasma proteins.⁷

Metabolism

The expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.⁷

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 25 days.^6,7

Clearance

Vedolizumab clearance depends on both linear and nonlinear pathways; the nonlinear clearance decreases with increasing concentrations. Population pharmacokinetic analyses indicated that the linear clearance was approximately 0.157 L/day or 0.180 to 0.266 ml/hr/kg.^6,7

Adverse Effects

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Toxicity

Elevated transaminase levels with or without elevated bilirubin have occurred in patients who have received this drug. Progressive multifocal leukoencephalopathy (PML) has not been reported with the 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.⁶ The use of vedolizumab may increase the risk of developing infections, and one study found that nasopharyngitis occurs more frequently with vedolizumab than with THE placebo for Crohn’s disease patients.⁴

Available pharmacovigilance data, data from the ongoing pregnancy registry, and data from published case reports and cohort studies in pregnant women have not identified a vedolizumab-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with inflammatory bowel disease in pregnancy. No fetal harm was observed in animal reproduction studies with intravenous administration of vedolizumab to rabbits and monkeys at dose levels 20 times the recommended human dosage.⁶

Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth.⁶

Vedolizumab administered during pregnancy could affect immune responses in the in-utero-exposed newborn and infant. The clinical significance of low levels of vedolizumab in utero-exposed infants is unknown. The safety of administering live or live-attenuated vaccines in exposed infants is unknown.⁶

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of vedolizumab. Studies to evaluate the possible impairment of fertility or mutagenic potential of vedolizumab have not been performed.⁶

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
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Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Vedolizumab.
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Vedolizumab.
Adalimumab	The risk or severity of infection can be increased when Adalimumab is combined with Vedolizumab.
Adenovirus type 7 vaccine live	The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Vedolizumab.
Aducanumab	The risk or severity of adverse effects can be increased when Vedolizumab is combined with Aducanumab.
Aldesleukin	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Vedolizumab.
Alefacept	The risk or severity of adverse effects can be increased when Alefacept is combined with Vedolizumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Vedolizumab.
Alirocumab	The risk or severity of adverse effects can be increased when Vedolizumab is combined with Alirocumab.
Allogeneic processed thymus tissue	The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Vedolizumab.

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Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Entyvio	Injection, solution	108 mg	Subcutaneous	Takeda Pharma A/S	2021-02-10	Not applicable
Entyvio	Solution	108 mg / 0.68 mL	Subcutaneous	Takeda	2020-07-08	Not applicable
Entyvio	Injection, solution	108 mg	Subcutaneous	Takeda Pharma A/S	2021-02-10	Not applicable
Entyvio	Injection, powder, lyophilized, for solution	300 mg/5mL	Intravenous	Takeda Pharmaceuticals America, Inc.	2014-05-20	Not applicable
Entyvio	Injection, solution	108 mg	Subcutaneous	Takeda Pharma A/S	2021-02-10	Not applicable
Entyvio	Solution	108 mg / 0.68 mL	Subcutaneous	Takeda	2020-11-20	Not applicable
Entyvio	Injection, solution	108 mg	Subcutaneous	Takeda Pharma A/S	2021-02-10	Not applicable
Entyvio	Injection, solution	108 mg	Subcutaneous	Takeda Pharma A/S	2021-02-10	Not applicable
Entyvio	Injection, powder, for solution	300 mg	Intravenous	Takeda Pharma A/S	2016-09-08	Not applicable
Entyvio	Powder, for solution	300 mg / vial	Intravenous	Takeda	2015-04-21	Not applicable

Chemical Identifiers

UNII: 9RV78Q2002
CAS number: 943609-66-3

References

General References

Ardizzone S, Bianchi Porro G: Biologic therapy for inflammatory bowel disease. Drugs. 2005;65(16):2253-86. [Article]
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]
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]
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]
Cherry LN, Yunker NS, Lambert ER, Vaughan D, Lowe DK: Vedolizumab: an alpha4beta7 integrin antagonist for ulcerative colitis and Crohn's disease. Ther Adv Chronic Dis. 2015 Sep;6(5):224-33. doi: 10.1177/2040622315586970. [Article]
FDA Approved Drug Products: ENTYVIO (vedolizumab) for injection, for intravenous use [Link]
Assessment report: Entyvio (International non-proprietary name vedolizumab) [Link]
Takeda Announces FDA Acceptance of BLA Resubmission for Investigational Subcutaneous Administration of Entyvio® (vedolizumab) for Maintenance Therapy in Moderately to Severely Active Ulcerative Colitis [Link]
Takeda Announces FDA Acceptance of BLA for Subcutaneous Administration of ENTYVIO® (vedolizumab) for Maintenance Therapy in Moderately to Severely Active Crohn’s Disease [Link]

External Links

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

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Crohn's Disease (CD) / Ulcerative Colitis	1
4	Completed	Treatment	Crohn's Disease (CD)	3
4	Completed	Treatment	Crohn's Disease (CD) / Ulcerative Colitis	2
4	Completed	Treatment	Pouchitis	1
4	Completed	Treatment	Ulcerative Colitis	2
4	Not Yet Recruiting	Treatment	Biologics / Mesalazine / Self Efficacy / Ulcerative Colitis	1
4	Recruiting	Prevention	Crohn's Disease (CD)	1
4	Recruiting	Treatment	Crohn Disease of Small Intestine	1
4	Recruiting	Treatment	Crohn's Disease (CD) / Inflammatory Bowel Diseases (IBD) / Ulcerative Colitis	1
4	Recruiting	Treatment	Ulcerative Colitis	4

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Intravenous
Injection, powder, for solution	Intravenous	300 mg
Injection, powder, for solution	Intravenous; Parenteral	300 MG
Injection, powder, lyophilized, for solution	Intravenous	300 mg/5mL
Injection, solution	Subcutaneous	108 MG
Powder, for solution	Intravenous	300 mg / vial
Solution	Intravenous	300.000 mg
Solution	Subcutaneous	108 mg / 0.68 mL
Powder	Intravenous	300 mg
Injection, powder, lyophilized, for solution	Intravenous
Solution	Subcutaneous	108.00 mg
Injection, solution, concentrate	Intravenous	300 mg/1vial

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US2012151248	No	2012-05-02	2032-05-02

Properties

State

Solid

Experimental Properties

Property	Value	Source
isoelectric point	7.6-8.3	European Medicines Agency Assessment Report (Procedure No.: EMEA/H/C/002782/0000)

Targets

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Details1. Integrin alpha-4

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

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]
FDA Approved Drug Products: ENTYVIO (vedolizumab) for injection, for intravenous use [Link]

Details2. Integrin beta-7

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

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]
FDA Approved Drug Products: ENTYVIO (vedolizumab) for injection, for intravenous use [Link]

Drug created at February 20, 2015 22:30 / Updated at September 24, 2023 02:55

Vedolizumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References