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| Primary information |
|---|
| ID | 14942 |
| Therapeutic ID | Th1554 |
| Protein Name | Enfortumab vedotin |
| Sequence | NA
|
| Molecular Weight | 152000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The elimination half-lives of enfortumab vedotin and MMAE are 3.4 days and 2.4 days, respectively.[L10836] |
| Description | Enfortumab vedotin is an antibody-drug conjugate used in the treatment of patients with advanced, treatment-resistant urothelial cancers.[L10836] 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.[L10836] 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[A188868] and it was first approved for use in the United States in December 2019 under the brand name PadcevTM.[L10836] |
| Indication/Disease | 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 a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.[L10836] |
| Pharmacodynamics | Enfortumab vedotin is an anti-cancer agent that destroys tumor cells by inhibiting their ability to replicate.[L10836] 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.[L10836] 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.[L10836] |
| Mechanism of Action | Enfortumab vedotin is an antibody-drug conjugate comprised of multiple components.[L10836] It contains a fully human monoclonal antibody directed against Nectin-4, an extracellular adhesion protein which is highly expressed in urothelial cancers,[A188865] 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.[L10836] |
| 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.[L10836] Symptomatic and supportive measures are recommended. |
| Metabolism | The catabolism of enfortumab vedotin has not been studied in humans.[L10836] 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_.[L10836] |
| 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.[L10836] The Tmax of MMAE is 1-3 days following the end of the infusion.[A188865] |
| The estimated steady-state volume of distribution is 11 L.[L10836] |
| Clearance | The mean clearance of enfortumab vedotin and free MMAE was 0.10 L/h and 2.7 L/h, respectively.[L10836] The clearance of MMAE appears to be limited by its rate of release from enfortumab vedotin. |
| Categories | Blood Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Nectin-4 |
| Brand Name | Padcev Ejfv |
| Company | Seagen Inc. |
| Brand Description | Seagen Inc. |
| Prescribed For | Intravenous |
| Chemical Name | 30 mg/3mL |
| Formulation | None. |
| Physical Appearance | received an immunotherapy medicine and also received a chemotherapy-containing platinum medicine. |
| Route of Administration | It is given as an infusion (drip) into a vein over 30 minutes. The patient should have an infusion three times over the course of 28 days (on days 1, 8 and 15) and should continue treatment until the disease gets worse or the side effects become intolerable. |
| Recommended Dosage | The active substance in Padcev, enfortumab vedotin, consists of an antibody (a type of protein) combined with another substance known as MMAE. The antibody first attaches to a protein on the surface of cancer cells to gain entry into the cells. Once the active substance is inside the cells, MMAE disrupts the cells’ internal skeleton, causing cell death and helping to stop the cancer from getting worse or spreading. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |