Policy & Regulation
Exelixis Partner Takeda Receives Approval in Japan for Cabometyx Tablets for the Treatment of Curatively Unresectable or Metastatic Renal Cell Carcinoma
25 March 2020 - - US-based oncology-focused biotechnology company Exelixis, Inc.'s (NASDAQ: EXEL) partner for the clinical development and commercialization of Cabometyx (cabozantinib) in Japan, Japan-based Takeda Pharmaceutical Company Ltd, has received approval from the Japanese Ministry of Health, Labor and Welfare to manufacture and market Cabometyx as a treatment for patients with curatively unresectable or metastatic renal cell carcinoma, the company said.

The approval is based on the results of three clinical trials: METEOR, the Exelixis-sponsored phase 3 pivotal trial of cabozantinib versus everolimus in patients with advanced RCC that experienced disease progression following treatment with at least one prior VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI); CABOSUN, the Alliance for Clinical Trials in Oncology-sponsored phase 2 trial comparing cabozantinib with sunitinib in patients with previously untreated advanced RCC with intermediate- or poor-risk disease; and Cabozantinib-2001, a Takeda-sponsored phase 2 trial in 35 Japanese patients with advanced RCC who had progressed after prior VEGFR-TKI therapy.

Per the terms of Exelixis and Takeda's collaboration and license agreement, Exelixis is eligible to receive a USD 31m milestone payment from Takeda upon the first commercial sale of Cabometyx for unresectable or metastatic RCC.

In January 2020, Takeda applied for approval to manufacture and sell cabozantinib as a treatment for patients with unresectable hepatocellular carcinoma that had progressed after prior systemic therapy in Japan, which triggered a USD 10m milestone payment.

Exelixis will also be eligible to receive further development, regulatory and first-sale milestone payments of up to USD 45m from Takeda related both to previously treated and untreated RCC and previously treated HCC.

Exelixis continues to be eligible to receive additional development, regulatory and first-sale milestones for potential future cabozantinib indications and is also eligible for sales revenue milestones and royalties on net sales of cabozantinib in Japan.

Takeda fully funds cabozantinib development activities that are exclusively for the benefit of Japan and is responsible for 20% of the costs associated with global cabozantinib clinical trials, providing the company opts into those trials.

The American Cancer Society's 2020 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer in the US and estimate nearly 74,000 cases will be diagnosed this year.

The most common type of kidney cancer in adults is RCC, which accounts for about 90% of cases.

If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12%, with no identified cure.

Approximately 32,000 patients in the US and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2020, with an estimated 15,000 patients in the US in need of a first-line treatment.

About 70% of RCC cases are known as "clear cell" carcinomas, based on histology.

The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.

These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.

MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.

In the US, Cabometyx tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib.

Cabometyx tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide.

In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan.

In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical company Ltd. for the commercialization and further clinical development of cabozantinib for all future indications in Japan.