FDA Grants Priority Review to Astellas' sBLA for PADCEV® (enfortumab vedotin) Plus KEYTRUDA® (pembrolizumab) for First-Line Treatment of Locally Advanced or Metastatic Urothelial Cancer

Recently, Astellas Pharma, Inc. and Seagen, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted the priority review request for the supplemental Biologics License Application (sBLA) for PADCEV® (enfortumab vedotin-ejfv) in combination with KEYTRUDA® (pembrolizumab) as a treatment for adult patients with locally advanced or metastatic urothelial cancer (la/mUC), a type of bladder cancer that has spread to nearby organs, muscle, or other parts of the body.

According to the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of May 9, 2024. The FDA reviewed the application through its Real-Time Oncology Review (RTOR) pilot program, which aims to explore more efficient review processes to ensure safe and effective treatments are available to patients as early as possible. If approved, this combination therapy will become the preferred treatment option for both cisplatin-tolerant and cisplatin-intolerant patients.

It is estimated that approximately 82,290 patients in the United States will be diagnosed with bladder cancer in 2023. i Urothelial carcinoma accounts for 90% of all bladder cancer cases and can also occur in the renal pelvis, ureter, and urethra. ii About 12% of cases are locally advanced or metastatic urothelial carcinoma (la/mUC) at the time of diagnosis. iii The condition of most patients with la/mUC will deteriorate within nine months, and long-term survival rates are very low. iv

The sBLA for the use of combination therapy in first-line treatment is based on the results of the EV-302 Phase 3 clinical study (also known as KEYNOTE-A39). The study confirmed that the combination therapy improved overall survival (OS) and progression-free survival (PFS) in previously untreated patients with locally advanced or metastatic urothelial carcinoma (la/mUC), with results that were both statistically significant and clinically meaningful. The safety findings were consistent with previously reported results for the combination therapy, with no new safety concerns identified.

In February 2020, the combination therapy of PADCEV and KEYTRUDA received the FDA's "Breakthrough Therapy" designation. In December 2022, EV-103sBLA was granted priority review status. In April 2023, based on the tumor response rate and durability of response from the EV-103 trial, the FDA granted accelerated approval for the use of PADCEV in combination with KEYTRUDA to treat adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin. The EV-302 trial is designed to serve as the confirmatory trial for the accelerated approval of this combination therapy in the United States and to provide a basis for global registration applications, while also expanding the indication to include patients who are eligible for cisplatin.

About EV-302

EV-302 Trial

The EV-302 trial is part of a comprehensive program evaluating the efficacy of this combination therapy in treating urothelial cancer and other solid tumors across multiple stages. The results of the EV-302 trial were presented at the 2023 European Society for Medical Oncology (ESMO) Congress on October 2023.

About Enfortumab Vedotin

Enfortumab Vedotin is a first-in-class, direct-targeting antibody-drug conjugate that acts on Nectin-4, a protein located on the cell surface that is highly expressed in bladder cancer. Non-clinical data show that the anticancer activity of Enfortumab Vedotin is due to its binding to cells expressing the Nectin-4 protein, followed by the internalization and release of the antitumor agent monomethyl auristatin E (MMAE) into the cells, leading to cell cycle arrest and programmed cell death (apoptosis).

Editor: Mu Mian

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