Astellas' First-in-Class ADC Enfortumab Vedotin Granted Clinical Trial Clearance in China for Locally Advanced or Metastatic Urothelial Cancer

CDE’s Latest Announcement: Astellas’ Enfortumab Vedotin for Injection Receives Two Implicit Approvals for Clinical Trials, Intended for Development in Locally Advanced or Metastatic Urothelial CarcinomaPublic information indicates that this is a first-in-class antibody-drug conjugate (ADC) targeting Nectin-4. It has previously been granted Breakthrough Therapy Designation and Priority Review by the U.S. FDA, and was approved for marketing in the United States in late 2019 for the treatment of patients with locally advanced or metastatic urothelial carcinoma.

Screenshot source: CDE official website

Enfortumab vedotin is an antibody-drug conjugate developed jointly by Seagen and Astellas, comprising an anti-Nectin-4 monoclonal antibody linked to the microtubule-disrupting agent MMAE. Nectin-4 is a cell adhesion molecule expressed on the surface of various solid tumors, with particularly high expression in urothelial carcinoma.

In the United States, the FDA approved enfortumab vedotin for marketing in late 2019 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based chemotherapy and PD-1/PD-L1 inhibitors. In clinical studies, this product demonstrated an objective response rate (ORR) of 44% in 125 patients with advanced bladder cancer, including a complete response rate of 12%. It is important to note that these patients had extremely limited treatment options, being virtually “untreatable.” This FDA approval established enfortumab vedotin as a novel paradigm for treating patients with advanced urothelial carcinoma whose disease progressed after chemotherapy and immunotherapy.

Source: CDE Official Website

In China, Astellas and other companies submitted two clinical trial applications for injectable enfortumab vedotin in October this year, which were accepted. These applications correspond to the clinical trials now approved for locally advanced or metastatic urothelial carcinoma. Just yesterday, Astellas and others submitted two additional clinical trial applications for this product, indicating that the clinical development of this therapy is accelerating in China.

Notably, the combination therapy of enfortumab vedotin and the PD-1 inhibitor pembrolizumab has also received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for use as a first-line treatment in previously untreated patients with locally advanced or metastatic urothelial carcinoma.

Globally, approximately 580,000 people were diagnosed with bladder cancer in 2020. Urothelial carcinoma accounts for 90% of all bladder cancers and can also occur in the renal pelvis, ureters, and urethra. After failing initial platinum-based chemotherapy, 80% of patients with advanced disease do not respond to PD-1 or PD-L1 inhibitor therapy. These patients urgently need new treatment options.

References:

[1] Center for Drug Evaluation (CDE), National Medical Products Administration of China. Retrieved Dec 15, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] FDA approves new type of therapy to treat advanced urothelial cancer. Retrieved December 18, 2019, from https://www.fda.gov/news-events/press-announcements/fda-approves-new-type-therapy-treat-advanced-urothelial-cancer

[3] Seattle Genetics and Astellas Announce PADCEV® (enfortumab vedotin-ejfv) Significantly Improved Overall Survival in Phase 3 Trial in Previously Treated Locally Advanced or Metastatic Urothelial Cancer. Retrieved September 18, 2020, from https://www.businesswire.com/news/home/20200918005101/en

Source: Yiyao Guanlan

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