The Food and Drug Administration (FDA) has granted accelerated approval to Padcev (enfortumab vedotin-ejfv; Seattle Genetics and Astellas Pharma) for the treatment of locally advanced or metastatic urothelial cancer in adult patients who have previously received a programmed death receptor-1 (PD-1) or programmed death ligand (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.
Padcev is a first-in-class antibody-drug conjugate (ADC) directed against Nectin-4, an adhesion protein located on the surface of cells. Based on nonclinical data, Padcev demonstrates anticancer activity through the binding of the ADC to Nectin-4-expressing cells causing the release of the small molecule microtubule disrupting agent, MMAE, via proteolytic cleavage. The release of MMAE leads to cell cycle arrest and apoptosis.
The approval was based on data from the phase 2, single-arm, multicenter, EV-201 trial of Padcev in 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy. Results showed a confirmed objective response rate (primary end point) of 44% with Padcev (95% CI: 35.1, 53.2); 12% of patients experienced a complete response and 32% experienced a partial response. The median duration of response, a secondary end point, was 7.6 months (95% CI: 6.3, not estimable [NE]).
With regard to safety, the most common adverse reactions observed included fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, dysgeusia, diarrhea, dry eye, pruritus and dry skin. In addition, the prescribing information for Padcev includes warnings and precautions regarding hyperglycemia, peripheral neuropathy, ocular disorders, skin reactions, embryo-fetal toxicity and infusion site extravasation.
“Metastatic urothelial cancer is an aggressive and devastating disease with limited treatment options, and the approval of Padcev is a significant advance for these patients who previously had limited options after initial therapies failed,” said Jonathan E. Rosenberg, MD, Medical Oncologist, Chief, Genitourinary Medical Oncology Service, Memorial Sloan Kettering Cancer Center in New York. “The Padcev clinical trial enrolled a range of patients whose cancer was difficult to treat, including those whose disease had spread to the liver.”
As part of the accelerated approval process, the Company is conducting the ongoing phase 3 EV-301 trial to confirm the clinical benefit of Padcev. The FDA previously granted Priority Review and Breakthrough Therapy designations to Padcev for this indication.
The product is supplied as 20mg and 30mg single-dose vials for intravenous infusion after reconstitution.