On April 13, 2022 Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (Nasdaq:SGEN) reported that the European Commission (EC) has approved PADCEV (enfortumab vedotin) as monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a PD-1/L1 inhibitor (Press release, Seagen, APR 13, 2022, View Source [SID1234612139]). The EC approval is supported by data from the global phase 3 EV-301 trial that demonstrated an overall survival (OS) benefit compared with chemotherapy.

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"The approval of enfortumab vedotin in the European Union is a significant milestone for people living with advanced urothelial cancer who have had limited treatment options and poor survival rates," said Ahsan Arozullah, M.D., M.P.H., Vice President, Medical Sciences-Oncology, Astellas. "We look forward to working with health authorities to ensure people living with advanced urothelial cancer can access this new treatment option as soon as possible."

The EV-301 trial compared enfortumab vedotin to chemotherapy in adult patients (n=608) with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. At the time of the pre-specified interim analysis, patients who received enfortumab vedotin (n=301) in the trial lived a median of 3.9 months longer than those who received chemotherapy (n=307). Median OS was 12.9 vs. 9 months, respectively [Hazard Ratio=0.70 (95% Confidence Interval [CI]: 0.56, 0.89), p=0.001]. Across clinical trials, the most common adverse reactions with enfortumab vedotin were alopecia, fatigue, decreased appetite, peripheral sensory neuropathy, diarrhea, nausea, pruritus, dysgeusia, anemia, weight decreased, rash maculo-papular, dry skin, vomiting, aspartate aminotransferase increased, hyperglycemia, dry eye, alanine aminotransferase increased and rash.

"The EV-301 study is the first randomized trial to show improved overall survival in patients with advanced urothelial cancer who received a platinum-containing chemotherapy and an immunotherapy," said Professor Ignacio Durán, M.D., Ph.D., Hospital Universitario Marqués de Valdecilla, Spain. "This approval of enfortumab vedotin from the European Commission is an important moment for these patients and their physicians."

Results from the EV-301 trial are intended to support global registrations for enfortumab vedotin. The EC marketing authorization for enfortumab vedotin is applicable in the European Union (EU) Member States, as well as Iceland, Norway and Liechtenstein.1

Urothelial cancer is the most common type of bladder cancer.2 In Europe, an estimated 204,000 people were diagnosed with urothelial cancer in 2020, and more than 67,000 died as a result of the disease.3 Enfortumab vedotin is the first antibody-drug conjugate authorized in the EU for people living with urothelial cancer.

About Urothelial Cancer

Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.2 Globally, approximately 573,000 new cases of bladder cancer and 212,000 deaths are reported annually.3

About the EV-301 Trial

The EV-301 trial (NCT03474107) was a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in 608 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies.4 The primary endpoint was overall survival and secondary endpoints included progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters. Results were published in the New England Journal of Medicine.

About PADCEV (enfortumab vedotin)

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5,6 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).5 PADCEV is co-developed by Astellas and Seagen.

Important Safety Information

The full European Summary of Product Characteristics (SmPC) for PADCEV will be available from the European Medicines Agency website at www.ema.europa.eu.