– Submission based on two clinical trials in patients with advanced hepatocellular carcinoma who had received prior systemic therapy –
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 CABOMETYX® (cabozantinib) in Japan, has applied to the Japanese Ministry of Health, Labor and Welfare (MHLW) for Manufacturing and Marketing Approval of cabozantinib as a treatment for patients with unresectable hepatocellular carcinoma (HCC) that had progressed after prior systemic therapy.
Takeda’s application is based on the results of two clinical trials in patients with advanced HCC who had received prior systemic therapy: CELESTIAL (XL184-309), a global, randomized, placebo-controlled, double-blind phase 3 clinical trial, and Cabozantinib-2003, a phase 2 clinical trial conducted in Japan.
“We are excited about the progress our partner Takeda has made on advancing cabozantinib toward regulatory approval in Japan for patients with advanced liver cancer,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “This regulatory filing is an important milestone for patients in Japan who currently have limited treatment options after they have progressed following systemic therapy. We look forward to our continued collaboration as Takeda works to bring cabozantinib to patients in need of new therapies.”
Per the terms of Exelixis and Takeda’s collaboration and license agreement, Exelixis is eligible to receive a $10 million milestone payment from Takeda as a result of this latest submission for HCC, which is anticipated to be received in the first quarter of 2020. In April 2019, Takeda applied for approval to manufacture and sell cabozantinib as a treatment for unresectable and metastatic renal cell carcinoma (RCC) in Japan. Following the milestone associated with this HCC regulatory filing, Exelixis will be eligible to receive further development, regulatory and first-sale milestone payments of up to $76 million from Takeda related both to previously treated and previously 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.
About HCC
Liver cancer is a leading cause of cancer death worldwide, accounting for more than 700,000 deaths and 800,000 new cases each year.1 In the U.S., the incidence of liver cancer has more than tripled since 1980.2 HCC is the most common form of liver cancer, making up about three-fourths of the estimated 43,000 new cases in the U.S. in 2020.2 HCC is the fastest-rising cause of cancer-related death in the U.S.3 Without treatment, patients with advanced HCC usually survive less than 6 months.4
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 Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan.
Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
U.S. Important Safety Information
- Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
- Perforations and Fistulas: Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
- Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.
- Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and