Identification

Summary

Polatuzumab vedotin is a CD79b antibody conjugate indicated to treat relapsed or refractory B-cell lymphoma.

Brand Names
Polivy
Generic Name
Polatuzumab vedotin
DrugBank Accession Number
DB12240
Background

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

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
Protein Chemical Formula
Not Available
Protein Average Weight
149987.0 Da (Approximate, Complex)
Sequences
Not Available
Synonyms
  • Polatuzumab vedotin
  • polatuzumab vedotin-piiq

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

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Associated Conditions
Contraindications & Blackbox Warnings
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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
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

Adverse Effects
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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

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
AbametapirThe serum concentration of Polatuzumab vedotin can be increased when it is combined with Abametapir.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Polatuzumab vedotin.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Polatuzumab vedotin.
AducanumabThe risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Aducanumab.
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.
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Polatuzumab vedotin.
AmivantamabThe risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Amivantamab.
AmprenavirThe risk or severity of adverse effects can be increased when Amprenavir is combined with Polatuzumab vedotin.
AnifrolumabThe risk or severity of adverse effects can be increased when Anifrolumab is combined with Polatuzumab vedotin.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PolivyPowder, for solution30 mg / vialIntravenousHoffmann La Roche2021-10-26Not applicableCanada flag
PolivyInjection, powder, lyophilized, for solution140 mg/7.52mLIntravenousGenentech, Inc.2019-06-10Not applicableUS flag
PolivyInjection, powder, for solution30 mgIntravenousRoche Registration Gmb H2021-01-12Not applicableEU flag
PolivyPowder, for solution140 mg / vialIntravenousHoffmann La Roche2020-11-25Not applicableCanada flag
PolivyInjection, powder, for solution140 mgIntravenousRoche Registration Gmb H2021-01-12Not applicableEU flag
PolivyInjection, powder, lyophilized, for solution30 mg/1.88mLIntravenousGenentech, Inc.2019-06-10Not applicableUS flag

Categories

ATC Codes
L01FX14 — Polatuzumab vedotin
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
KG6VO684Z6
CAS number
1313206-42-6

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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. FDA Approved Drug Products: Polivy [Link]
PubChem Substance
347911301
RxNav
2174091
Wikipedia
Polatuzumab_vedotin
FDA label
Download (695 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
3CompletedTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
3RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
3RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
3RecruitingTreatmentRefractory Diffuse Large B Cell Lymphoma (DLBCL) / Relapsed Diffuse Large B-cell Lymphoma (DLBCL)1
2Not Yet RecruitingTreatmentAggressive Non-hodgkin Lymphoma (aNHL) / Non-Hodgkin's Lymphoma, Relapsed / Refractory Non-Hodgkin's lymphoma1
2Not Yet RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
2Not Yet RecruitingTreatmentFollicular Lymphoma ( FL)1
2Not Yet RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2RecruitingTreatmentB Cell Lymphoma (BCL) / Diffuse Large B-Cell Lymphoma (DLBCL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous140 mg
Injection, powder, for solutionIntravenous30 MG
Injection, powder, lyophilized, for solutionIntravenous140 mg/7.52mL
Injection, powder, lyophilized, for solutionIntravenous30 mg/1.88mL
Injection, solution, concentrateIntravenous140 mg/1vial
Powder, for solutionIntravenous140 mg / vial
Powder, for solutionIntravenous30 mg / vial
Powder140 mg
Injection, powder, lyophilized, for solutionIntravenous140 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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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 at October 20, 2016 21:42 / Updated at June 03, 2022 07:24