Enfortumab vedotin
Identification
- Summary
Enfortumab vedotin is an antibody-drug conjugate comprised of a fully human monoclonal antibody and microtubule-disrupting chemotherapeutic agent used in the treatment of advanced or metastatic urothelial cancer.
- Brand Names
- Padcev
- Generic Name
- Enfortumab vedotin
- DrugBank Accession Number
- DB13007
- Background
Enfortumab vedotin is an antibody-drug conjugate used in the treatment of patients with advanced, treatment-resistant urothelial cancers.3 It is comprised of a fully human monoclonal antibody targeted against Nectin-4 and a microtubule-disrupting chemotherapeutic agent, monomethyl auristatin E (MMAE), joined by a protease-cleavable link.3 It is similar to brentuximab vedotin, another antibody conjugated with MMAE that targets CD-30 instead of Nectin-4.
The clinical development of enfortumab vedotin was the result of a collaboration between Astellas Pharma and Seattle Genetics 2 and it was first approved for use in the United States in December 2019 under the brand name PadcevTM.3 Enfortumab vedotin was later approved by the European Commission on April 13, 2022.5
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 152000.0 Da
- Sequences
- Not Available
- Synonyms
- Enfortumab vedotin
- enfortumab vedotin-ejfv
- External IDs
- AGS-22M6E
Pharmacology
- Indication
Enfortumab vedotin is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.3,4 Enfortumab vedotin can also be indicated in combination with pembrolizumab in adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy under accelerated approval from the FDA.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Locally advanced urothelial cancer •••••••••••• ••••• •••••••• ••••••• •••• •••••••••• ••••• •••••••••• •••••• •• •••••••••• •••••••••••• • ••••••• •••••••••• •••••••• •••••••••••••• •••••••••••• ••••••••• Used in combination to treat Locally advanced or metastatic urothelial carcinoma (uc) Regimen in combination with: Pembrolizumab (DB09037) •••••••••••• ••••• ••••••••• Treatment of Metastatic urothelial cancer •••••••••••• ••••• •••••••• ••••••• •••• •••••••••• ••••• •••••••••• •••••• •• •••••••••• •••••••••••• • ••••••• •••••••••• •••••••• •••••••••••••• •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Enfortumab vedotin is an anti-cancer agent that destroys tumor cells by inhibiting their ability to replicate.3 Patients with moderate to severe hepatic impairment should not use enfortumab vedotin - although it has not been studied in this population, other MMAE-containing antibody-drug conjugates have demonstrated increased rates of adverse effects in patients with moderate-severe hepatic impairment.3 Enfortumab vedotin may also cause significant hyperglycemia leading, in some cases, to diabetic ketoacidosis, and should not be administered to patients with a blood glucose level >250 mg/dl.3
- Mechanism of action
Enfortumab vedotin is an antibody-drug conjugate comprised of multiple components.3 It contains a fully human monoclonal antibody directed against Nectin-4, an extracellular adhesion protein which is highly expressed in urothelial cancers,1 attached to a chemotherapeutic microtubule-disrupting agent, monomethyl auristatin E (MMAE). These two components are joined via a protease-cleavable linker. Enfortumab vedotin binds to cells expressing Nectin-4 and the resulting enfortumab-Nectin-4 complex is internalized into the cell. Once inside the cell, MMAE is released from enfortumab vedotin via proteolytic cleavage and goes on to disrupt the microtubule network within the cell, arresting the cell cycle and ultimately inducing apoptosis.3
Target Actions Organism UNectin-4 binderantibodyHumans - Absorption
Following the first treatment cycle, Cmax and AUC0-28d for enfortumab vedotin were 28 µg/mL and 111 µg.d/mL, respectively. The Cmax and AUC0-28d of unconjugated MMAE following the same cycle were 4.8 ng/mL and 69 ng.d/mL, respectively.3 The Tmax of MMAE is 1-3 days following the end of the infusion.1
- Volume of distribution
The estimated steady-state volume of distribution is 11 L.3
- Protein binding
MMAE was found to be 68-82% protein-bound in vitro.3 The specific proteins to which MMAE is bound have not been elucidated.
- Metabolism
The catabolism of enfortumab vedotin has not been studied in humans.3 Given its structure, it is expected to be catabolized to smaller peptides, amino acids, unconjugated MMAE, and MMAE metabolites. MMAE is released from enfortumab vedotin via proteolytic cleavage by intracellular proteases and is metabolized primarily by CYP3A4 in vitro.3
- Route of elimination
Excretion kinetics have not been fully characterized, but may be extrapolated from data available from another MMAE-containing antibody-drug conjugate - kinetic studies of this drug demonstrated that 17% of the total MMAE administered was recovered in feces, and 6% was recovered in urine, primarily as unchanged drug, over a 1-week period.3
- Half-life
The elimination half-lives of enfortumab vedotin and MMAE are 3.4 days and 2.4 days, respectively.3
- Clearance
The mean clearance of enfortumab vedotin and free MMAE was 0.10 L/h and 2.7 L/h, respectively.3 The clearance of MMAE appears to be limited by its rate of release from enfortumab vedotin.
- Adverse Effects
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- Toxicity
Toxicity information regarding enfortumab vedotin is not readily available. Patients experiencing an overdose are likely at an increased risk of severe adverse effects such as significant nausea, vomiting, neuropathy, or rash.3 Symptomatic and supportive measures are recommended.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Enfortumab vedotin can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Enfortumab vedotin. Abrocitinib The serum concentration of Enfortumab vedotin can be increased when it is combined with Abrocitinib. Adagrasib The serum concentration of Enfortumab vedotin can be increased when it is combined with Adagrasib. Afatinib The serum concentration of Enfortumab vedotin can be increased when it is combined with Afatinib. - Food Interactions
- 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 Padcev Injection, powder, for solution 30 mg Intravenous Astellas Pharma Europe Bv 2022-05-11 Not applicable EU Padcev Powder, for solution 20 mg / vial Intravenous Seagen Inc. 2021-12-20 Not applicable Canada Padcev Injection, powder, for solution 20 mg Intravenous Astellas Pharma Europe Bv 2022-05-11 Not applicable EU Padcev Powder, for solution 30 mg / vial Intravenous Seagen Inc. 2023-01-10 Not applicable Canada Padcev Ejfv Injection, powder, lyophilized, for solution 30 mg/3mL Intravenous Seagen Inc. 2019-12-18 Not applicable US
Categories
- ATC Codes
- L01FX13 — Enfortumab vedotin
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antibody-drug Conjugates
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- Microtubule Inhibitors
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- Nectin-4-directed Antibodies
- P-glycoprotein substrates
- Proteins
- Serum Globulins
- 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
- Humans and other mammals
Chemical Identifiers
- UNII
- DLE8519RWM
- CAS number
- 1346452-25-2
References
- General References
- Hanna KS: Clinical Overview of Enfortumab Vedotin in the Management of Locally Advanced or Metastatic Urothelial Carcinoma. Drugs. 2019 Dec 10. pii: 10.1007/s40265-019-01241-7. doi: 10.1007/s40265-019-01241-7. [Article]
- McGregor BA, Sonpavde G: Enfortumab Vedotin, a fully human monoclonal antibody against Nectin 4 conjugated to monomethyl auristatin E for metastatic urothelial Carcinoma. Expert Opin Investig Drugs. 2019 Oct;28(10):821-826. doi: 10.1080/13543784.2019.1667332. Epub 2019 Sep 17. [Article]
- FDA Approved Drug Products: Padcev (enfortumab vedotin-ejfv) for IV injection [Link]
- EMA Approved Drug Products: Padcev (enfortumab vedotin) intravenous infusion [Link]
- Businesswise News: European Commission Approves PADCEV™ (enfortumab vedotin) for Locally Advanced or Metastatic Urothelial Cancer [Link]
- FDA Approved Drug Products: Padcev (enfortumab vedotin-ejfv) for IV injection (December 2023) [Link]
- Pfizer Press Release: PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) Approved by FDA as the First and Only ADC Plus PD-1 to Treat Advanced Bladder Cancer [Link]
- External Links
- PubChem Substance
- 347911415
- 2268306
- Wikipedia
- Enfortumab_vedotin
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Bladder Cancer 1 3 Active Not Recruiting Treatment Bladder Cancer / Ureteral Cancer / Urothelial Cancer 1 3 Recruiting Treatment Muscle Invasive Bladder Cancer 1 3 Recruiting Treatment Urinary Bladder Cancer, Muscle-invasive 1 3 Recruiting Treatment Urothelial Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 20 mg Injection, powder, for solution Intravenous 30 mg Powder, for solution Intravenous 20 mg / vial Powder, for solution Intravenous 30 mg / vial Solution Intravenous 20.00 mg Injection, powder, lyophilized, for solution Intravenous 20 mg/2mL Injection, powder, lyophilized, for solution Intravenous 30 mg/3mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- BinderAntibody
- General Function
- Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells.
- Specific Function
- Cell adhesion molecule binding
- Gene Name
- NECTIN4
- Uniprot ID
- Q96NY8
- Uniprot Name
- Nectin-4
- Molecular Weight
- 55453.875 Da
References
- FDA Approved Drug Products: Padcev (enfortumab vedotin-ejfv) for IV injection [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- FDA Approved Drug Products: Padcev (enfortumab vedotin-ejfv) for IV injection [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: Padcev (enfortumab vedotin-ejfv) for IV injection [Link]
Drug created at October 21, 2016 02:01 / Updated at January 10, 2024 06:22