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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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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
Target Actions Organism AB-cell antigen receptor complex-associated protein beta chain Not Available Humans - 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Polatuzumab vedotin can be increased when it is combined with Abametapir. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Polatuzumab vedotin. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Polatuzumab vedotin. Aducanumab The risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Polatuzumab vedotin. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Polatuzumab vedotin. Amiodarone The risk or severity of adverse effects can be increased when Amiodarone is combined with Polatuzumab vedotin. Amivantamab The risk or severity of adverse effects can be increased when Polatuzumab vedotin is combined with Amivantamab. Amprenavir The risk or severity of adverse effects can be increased when Amprenavir is combined with Polatuzumab vedotin. Anifrolumab The risk or severity of adverse effects can be increased when Anifrolumab is combined with Polatuzumab vedotin. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Polivy Powder, for solution 30 mg / vial Intravenous Hoffmann La Roche 2021-10-26 Not applicable Canada 
Polivy Injection, powder, lyophilized, for solution 140 mg/7.52mL Intravenous Genentech, Inc. 2019-06-10 Not applicable US 
Polivy Injection, powder, for solution 30 mg Intravenous Roche Registration Gmb H 2021-01-12 Not applicable EU 
Polivy Powder, for solution 140 mg / vial Intravenous Hoffmann La Roche 2020-11-25 Not applicable Canada Polivy Injection, powder, for solution 140 mg Intravenous Roche Registration Gmb H 2021-01-12 Not applicable EU Polivy Injection, powder, lyophilized, for solution 30 mg/1.88mL Intravenous Genentech, Inc. 2019-06-10 Not applicable US
Categories
- ATC Codes
- L01FX14 — Polatuzumab vedotin
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- CD79b-directed Antibody–Drug Conjugates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Globulins
- Immunoglobulins
- Immunologic Factors
- Immunoproteins
- Immunotherapy
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- Noxae
- Proteins
- Serum Globulins
- Toxic Actions
- 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
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: Polivy [Link]
- External Links
- PubChem Substance
- 347911301
- 2174091
- Wikipedia
- Polatuzumab_vedotin
- FDA label
- Download (695 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Diffuse Large B-Cell Lymphoma (DLBCL) 1 3 Completed Treatment Diffuse Large B-Cell Lymphoma (DLBCL) 1 3 Recruiting Treatment Diffuse Large B-Cell Lymphoma (DLBCL) 1 3 Recruiting Treatment Non-Hodgkin's Lymphoma (NHL) 1 3 Recruiting Treatment Refractory Diffuse Large B Cell Lymphoma (DLBCL) / Relapsed Diffuse Large B-cell Lymphoma (DLBCL) 1 2 Not Yet Recruiting Treatment Aggressive Non-hodgkin Lymphoma (aNHL) / Non-Hodgkin's Lymphoma, Relapsed / Refractory Non-Hodgkin's lymphoma 1 2 Not Yet Recruiting Treatment Diffuse Large B-Cell Lymphoma (DLBCL) 1 2 Not Yet Recruiting Treatment Follicular Lymphoma ( FL) 1 2 Not Yet Recruiting Treatment Mantle Cell Lymphoma (MCL) 1 2 Recruiting Treatment B Cell Lymphoma (BCL) / Diffuse Large B-Cell Lymphoma (DLBCL) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 140 mg Injection, powder, for solution Intravenous 30 MG Injection, powder, lyophilized, for solution Intravenous 140 mg/7.52mL Injection, powder, lyophilized, for solution Intravenous 30 mg/1.88mL Injection, solution, concentrate Intravenous 140 mg/1vial Powder, for solution Intravenous 140 mg / vial Powder, for solution Intravenous 30 mg / vial Powder 140 mg Injection, powder, lyophilized, for solution Intravenous 140 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- 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
- 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