Vedolizumab

Identification

Name

Vedolizumab

Accession Number

DB09033

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.

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

Not Available

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.

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 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.

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%.

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

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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

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.
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.
Altretamine	The risk or severity of adverse effects can be increased when Altretamine is combined with Vedolizumab.
Amsacrine	The risk or severity of adverse effects can be increased when Amsacrine is combined with Vedolizumab.

Additional Data Available

Extended Description

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Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

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A severity rating for each drug interaction, from minor to major.

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Evidence Level

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A rating for the strength of the evidence supporting each drug interaction.

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Action

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An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Entyvio	Injection, powder, for solution	300 mg	Intravenous	Takeda Pharma A/S	2014-05-22	Not applicable
Entyvio	Solution	108 mg	Subcutaneous	Takeda	2020-07-08	Not applicable
Entyvio	Powder, for solution	300 mg	Intravenous	Takeda	2015-04-21	Not applicable
Entyvio	Injection, powder, lyophilized, for solution	300 mg/5mL	Intravenous	Takeda Pharmaceuticals America, Inc.	2014-05-20	Not applicable
Entyvio	Solution	108 mg	Subcutaneous	Takeda	Not applicable	Not applicable

Additional Data Available

Application Number

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A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

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A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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. [PubMed:16266194]
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]
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]
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
RxNav: 1538097
ChEMBL: CHEMBL1743087
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Vedolizumab

AHFS Codes

56:92.00 — Miscellaneous GI Drugs

FDA label

Download (281 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Crohn's Disease (CD)	1
4	Active Not Recruiting	Treatment	Crohn's Disease (CD) / Ulcerative Colitis	1
4	Active Not Recruiting	Treatment	Ulcerative Colitis	1
4	Completed	Treatment	Crohn's Disease (CD)	1
4	Completed	Treatment	Crohn's Disease (CD) / Ulcerative Colitis	1
4	Completed	Treatment	Ulcerative Colitis	2
4	Not Yet Recruiting	Basic Science	Inflammatory Bowel Diseases (IBD) / Psoriasis	1
4	Not Yet Recruiting	Treatment	Ulcerative Colitis	1
4	Recruiting	Treatment	Crohn Disease of Small Intestine	1
4	Recruiting	Treatment	Crohn's Disease (CD)	2

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Intravenous	300 mg
Injection, powder, for solution	Intravenous	300 MG/5ML
Injection, powder, for solution	Intravenous; Parenteral	300 MG
Injection, powder, lyophilized, for solution	Intravenous	300 mg/5mL
Injection, solution, concentrate	Intravenous	300 mg
Powder, for solution	Intravenous	300 mg
Solution	Subcutaneous	108 mg
Powder	Intravenous	300 mg
Injection, powder, lyophilized, for solution	Intravenous	300 mg

Prices

Not Available

Patents

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

Additional Data Available

Filed On

Available for Purchase

The date on which a patent was filed with the relevant government.

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Properties

State

Solid

Experimental Properties

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

Targets

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. [PubMed:19509315]

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. [PubMed:19509315]