Enfortumab vedotin-ejfv
Enfortumab vedotin-ejfv Uses, Dosage, Side Effects, Food Interaction and all others data.
Enfortumab vedotin-ejfv is an antibody-drug conjugate used in the treatment of patients with advanced, treatment-resistant urothelial cancers. 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. 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 and it was first approved for use in the United States in December 2019 under the brand name PadcevTM
Enfortumab vedotin-ejfv is an anti-cancer agent that destroys tumor cells by inhibiting their ability to replicate. 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. Enfortumab vedotin-ejfv 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.
| Trade Name | Enfortumab vedotin-ejfv |
| Generic | Enfortumab vedotin |
| Enfortumab vedotin Other Names | Enfortumab vedotin, enfortumab vedotin-ejfv |
| Type | Intravenous |
| Weight | 152000.0 Da |
| Protein binding | MMAE was found to be 68-82% protein-bound in vitro. The specific proteins to which MMAE is bound have not been elucidated. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Enfortumab vedotin-ejfv 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.
Enfortumab vedotin-ejfv 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 a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.
Enfortumab vedotin-ejfv is also used to associated treatment for these conditions: Locally Advanced Urothelial Cancer, Metastatic Urothelial Cancer
How Enfortumab vedotin-ejfv works
Enfortumab vedotin-ejfv is an antibody-drug conjugate comprised of multiple components. It contains a fully human monoclonal antibody directed against Nectin-4, an extracellular adhesion protein which is highly expressed in urothelial cancers, attached to a chemotherapeutic microtubule-disrupting agent, monomethyl auristatin E (MMAE). These two components are joined via a protease-cleavable linker. Enfortumab vedotin-ejfv 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.
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. Symptomatic and supportive measures are recommended.
Food Interaction
No interactions found.Volume of Distribution
The estimated steady-state volume of distribution is 11 L.
Elimination Route
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. The Tmax of MMAE is 1-3 days following the end of the infusion.
Half Life
The elimination half-lives of enfortumab vedotin and MMAE are 3.4 days and 2.4 days, respectively.
Clearance
The mean clearance of enfortumab vedotin and free MMAE was 0.10 L/h and 2.7 L/h, respectively. The clearance of MMAE appears to be limited by its rate of release from enfortumab vedotin.
Elimination Route
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.
Innovators Monograph
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