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| Primary information |
|---|
| ID | 14939 |
| 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 | Amino Acids, Peptides, and Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Nectin-4 |
| Brand Name | Padcev |
| Company | Seagen Inc. |
| Brand Description | Seagen Inc. |
| Prescribed For | Intravenous |
| Chemical Name | 20 mg / vial |
| Formulation | None. |
| Physical Appearance | fatigue, numbness and tingling in extremities, decreased appetite, rash, hair loss, nausea, changes in taste, diarrhea, dry eye, itching, dry skin, dry eye, and vomiting |
| Route of Administration | Padcev is an anticancer medicine that affects the growth and cell division of cancer cells. Padcev is a prescription medicine used to treat adults with cancer of the bladder or urinary tract (renal pelvis, ureter or urethra). Padcev is used when the cancer is advanced, has spread to other parts of the... |
| Recommended Dosage | PADCEV® is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) 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. |
| Contraindication | NA |
| Side Effects | These are not all of the possible side effects of PADCEV. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |