ALAMEDA, CALIF.--(BUSINESS WIRE)--
Exelixis, Inc. (Nasdaq: EXEL) today announced that Takeda Pharmaceutical Company Limited (Takeda), its partner responsible for the clinical development and commercialization of cabozantinib in Japan, has applied to the Japanese Ministry of Health, Labor and Welfare (MHLW) for approval to manufacture and sell CABOMETYX® (cabozantinib) as a treatment for unresectable and metastatic renal cell carcinoma (RCC) in the country. As a result of the submission, Exelixis will receive a $10 million milestone payment from Takeda, anticipated to be received in the second quarter of 2019.
Takeda’s application 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. Takeda’s phase 2 trial was the subject of a late-breaking abstract at the 107th Annual Meeting of the Japanese Urological Society on April 18, 2019.
“Takeda has proven to be a very effective partner in cabozantinib’s development program in Japan since the signing of our collaboration and licensing agreement in early 2017,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “This Japanese regulatory filing is an important milestone on the path toward offering CABOMETYX as a new therapeutic option for patients with unresectable, metastatic renal cell carcinoma in Japan. We congratulate our Takeda colleagues on the filing and look forward to further progress.”
Per the terms of Exelixis and Takeda’s collaboration and license agreement, Exelixis received a $50 million upfront payment at the time of signing. Following the milestone associated with this regulatory filing, Exelixis will be eligible to receive from Takeda further development, regulatory and first-sale milestone payments of up to $80 million related both to previously treated and previously untreated RCC and previously treated hepatocellular carcinoma (HCC), as well as additional development, regulatory and first-sale milestones for potential future cabozantinib indications. Exelixis 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. As of today, Takeda has opted into and is co-funding CheckMate 9ER, the ongoing phase 3 pivotal trial of cabozantinib plus nivolumab versus sunitinib in previously untreated advanced RCC.
The American Cancer Society’s 2019 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 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 percent, with no identified cure for the disease.1 Approximately 32,000 patients in the U.S. and 70,000 globally require treatment, and an estimated 15,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.3
The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.4,5 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.6,7,8,9 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.5,6
About CABOMETYX ® (cabozantinib)
In the U.S., 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 for the commercialization and further clinical development of cabozantinib for all future indications in Japan.
U.S. Important Safety Information
Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf .
Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model genetic systems, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four approved products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO™ (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of Standard & Poor’s (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.
This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis’ timing for receipt of a $10 million milestone payment from Takeda for Takeda’s submission of an application to the Japanese MHLW for approval to manufacture and sell CABOMETYX as a treatment for unresectable and metastatic RCC in Japan; the potential for CABOMETYX as a new therapeutic option for patients with unresectable and metastatic RCC in Japan; Exelixis’ eligibility for future development, regulatory and first-sale milestone payments, plus sales revenue milestones and royalties on net sales under its collaboration with Takeda; and Exelixis’ plans to reinvest in its business to maximize the potential of the company’s pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: risks and uncertainties related to regulatory review and approval processes, including that the Japanese MHLW may not approve CABOMETYX as a treatment for unresectable and metastatic RCC; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib; Exelixis’ dependence on its relationships with its collaboration partners, including their pursuit of regulatory approvals for cabozantinib in new indications; Exelixis’ ability to protect its intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting the ability of Exelixis and its partners to obtain regulatory approval for cabozantinib in new indications discussed under the caption “Risk Factors” in Exelixis’ Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 22, 2019, and in Exelixis’ future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein.
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.
1 American Cancer Society: Cancer Facts & Figures 2019. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. Accessed April 2019.
2 Jonasch, E., Gao, J., Rathmell, W., Renal cell carcinoma. BMJ. 2014; 349:g4797.
3 Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal data on file).
4 Harshman, L., and Choueiri, T. Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma. Cancer J. 2013; 19:316-323.
5 Rankin, et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci USA. 2014; 111:13373-13378.
6 Zhou, L., Liu, X-D., Sun, M., et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016; 35:2687-2697.
7 Koochekpour, et al. The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells. Mol Cell Biol. 1999; 19:5902–5912.
8 Takahashi, A., Sasaki, H., Kim, S., et al. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res. 1994; 54:4233-4237.
9 Nakagawa, M., Emoto, A., Hanada, T., Nasu, N., Nomura, Y. Tubulogenesis by microvascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma. Br J Urol. 1997; 79:681-687.
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