Identification

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Name
Polatuzumab vedotin
Accession Number
DB12240
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

Polatuzumab vedotin is a CD79b specific antibody conjugated to the antineoplastic agent monomethyl auristatin E.Label This medication was granted accelerated FDA approval on 10 June 2019.5

Protein chemical formula
Not Available
Protein average weight
149987.0 Da (Approximate, Complex)
Sequences
Not Available
Synonyms
  • polatuzumab vedotin-piiq
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PolivyInjection, powder, lyophilized, for solution140 mg/7.52mLIntravenousGenentech, Inc.2019-06-10Not applicableUs
Additional Data Available
  • Application Number
    Application Number

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

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  • Product Code
    Product Code

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

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Categories
UNII
KG6VO684Z6
CAS number
1313206-42-6

Pharmacology

Indication

This medication is indicated to treat adults with relapsed or refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab that has returned of progressed after 2 or more previous therapies.Label

Associated Conditions
Pharmacodynamics

The binding of the unconjugated drug to microtubules in B cells leads to a number of immunosuppressant adverse effects including neutropenia and thrombocytopenia.Label,2

The incidence of peripheral neuropathy also increases with increasing doses and time exposed to the drug.1

Polatuzumab vedotin does not prolong the QTc interval.

Mechanism of action

Polatuzumab vedotin is an antibody targeted to CD79b conjugated to the antineoplastic agent monomethyl auristatin E (MMAE).Label The antibody binds to CD79b on the surface of B cells, causing the conjugate to be endocytosed.Label Once inside the cell, lysosomal proteases cleave the link between MMAE and the antibody allowing MMAE to bind to microtubules, inhibit cell division, and induce apoptosis.Label

TargetActionsOrganism
AB-cell antigen receptor complex-associated protein beta chainNot AvailableHumans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Antibody conjugated monomethyl auristatin E (MMAE) reaches a maximum concentration of 803±233ng/mL while unconjugated MMAE reaches a maximum concentration of 6.82±4.73ng/mL.Label The area under the curve for the conjugated medication is 1860±966day*ng/mL and 52.3±18.0day*ng/mL for the unconjugated medication.Label

Because doses are delivered intravenously, a bioavailability value is not available.Label

Volume of distribution

The central volume of distribution is 3.15L.Label

Protein binding

In vitro studies of monomethyl auristatin E show that it is 71-77% bound to plasma proteins.Label

Metabolism

The metabolism of polatuzumab vedotin has not been studied in humans but is likely to be catabolized to small peptides, amino acids, unconjugated monomethyl auristatin E (MMAE), and metabolites of MMAE.Label MMAE is metabolized by cytochrome P450 3A4.Label

Route of elimination

The polatuzumab vedotin's antibody is likely to be metabolized into small peptides and amino acids meaning it's route of eliminate is likely to be mainly hepatic as it is a protein of approximately 150kDa.3

The conjugated antineoplastic agent, monomethyl auristatin E, is eliminated in the urine and feces.4

Half life

The antibody conjugated monomethyl auristatin E has a terminal half life of 12 days.Label

Clearance

0.9L/day.Label

Toxicity

Data regarding overdoses and LD50 are not readily available.

In animal studies, embryo-fetal morality and birth defects were observed at less than the recommended dose and so the risk to the fetus must be weighed against the benefit to the mother.Label There is currently no data for the effects of polatuzumab vedotin on human pregnancies, though women are advised to used contraception while taking this medication.Label

Women are advised not to breastfeed until 2 months after their last dose due to the potential risk to the infant, however no data is available regarding the effects of polatuzumab vedotin on the child or if it is present in breastmilk.Label

Studies have not been performed to determine the carcinogenicity of this medication.Label Monomethyl auristatine E (MMAE) appears to be genotoxic in in vivo experiments but is not mutagenic in any tests performed.Label Based on animal data, polatuzumab vedotin may adversely affect male fertility and it is not known if this effect would be reversible.Label

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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Polatuzumab vedotin.
AbituzumabThe risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Abrilumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Polatuzumab vedotin.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Polatuzumab vedotin.
AducanumabThe risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Polatuzumab vedotin.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Polatuzumab vedotin.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Polatuzumab vedotin.
AmatuximabThe risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Amatuximab.
Additional Data Available
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    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Lu D, Gillespie WR, Girish S, Agarwal P, Li C, Hirata J, Chu YW, Kagedal M, Leon L, Maiya V, Jin JY: Time-to-Event Analysis of Polatuzumab Vedotin-Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens. CPT Pharmacometrics Syst Pharmacol. 2017 Jun;6(6):401-408. doi: 10.1002/psp4.12192. Epub 2017 May 23. [PubMed:28544534]
  2. Tilly H, Morschhauser F, Bartlett NL, Mehta A, Salles G, Haioun C, Munoz J, Chen AI, Kolibaba K, Lu D, Yan M, Penuel E, Hirata J, Lee C, Sharman JP: Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Lancet Oncol. 2019 May 14. pii: S1470-2045(19)30091-9. doi: 10.1016/S1470-2045(19)30091-9. [PubMed:31101489]
  3. Tibbitts J, Canter D, Graff R, Smith A, Khawli LA: Key factors influencing ADME properties of therapeutic proteins: A need for ADME characterization in drug discovery and development. MAbs. 2016;8(2):229-45. doi: 10.1080/19420862.2015.1115937. Epub 2015 Dec 4. [PubMed:26636901]
  4. Han TH, Zhao B: Absorption, distribution, metabolism, and excretion considerations for the development of antibody-drug conjugates. Drug Metab Dispos. 2014 Nov;42(11):1914-20. doi: 10.1124/dmd.114.058586. Epub 2014 Jul 21. [PubMed:25048520]
  5. FDA Approved Drug Products: Polivy [Link]
External Links
PubChem Substance
347911301
Wikipedia
Polatuzumab_vedotin
FDA label
Download (695 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL) / Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia1
1RecruitingTreatmentB-cell Non-Hodgkin's Lymphomas1
1RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)2
1RecruitingTreatmentRelapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma1
1, 2Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma, Lymphoma, Non Hodgkin, Lymphoma, Follicular / Malignant Lymphomas1
1, 2Active Not RecruitingTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentDiffuse Large B-Cell Lymphoma, Lymphoma, Follicular / Follicular Lymphoma (FL) / Follicular Lymphoma, Diffuse Large B-Cell Lymphoma / Lymphoma, Follicular, Diffuse Large B-Cell Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2CompletedTreatmentLymphoma, B-Cell, Non-Hodgkin's Lymphoma / Non-Hodgkin's Lymphoma (NHL)1
1, 2RecruitingTreatmentB-cell Non-Hodgkin's Lymphomas1
3RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous140 mg/7.52mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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
Humans
Pharmacological action
Yes
General Function
Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation.
Specific Function
Identical protein binding
Gene Name
CD79B
Uniprot ID
P40259
Uniprot Name
B-cell antigen receptor complex-associated protein beta chain
Molecular Weight
26047.65 Da

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Monomethyl auristatin E, the drug conjugated to the antibody, is metabolized by CYP3A4.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Polotuzumab FDA label [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
The antibody targets the B-cell antigen receptor complex-associated protein beta chain which causes endocytosis of the drug-antibody complex.
General Function
Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation.
Specific Function
Identical protein binding
Gene Name
CD79B
Uniprot ID
P40259
Uniprot Name
B-cell antigen receptor complex-associated protein beta chain
Molecular Weight
26047.65 Da

Drug created on October 20, 2016 15:42 / Updated on December 02, 2019 09:21