Exelixis, Inc. announced that its partner Ipsen received validation of the application for variation to the Cabometyx (cabozantinib) Exelixis, Inc. announced that its partner Ipsen received validation of the application for variation to the Cabometyx (cabozantinib) marketing authorization from the European Medicines Agency (EMA), the European regulatory authority, for the addition of a new indication for patients with previously treated advanced hepatocellular carcinoma (HCC). The filing is based on results of the global pivotal phase 3 CELESTIAL trial, which met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with advanced HCC who had been previously treated with sorafenib (pre-specified critical p-value = 0.021).
“We are excited by the potential benefit Cabometyx may offer patients in the European Union diagnosed with previously treated advanced hepatocellular carcinoma, a patient community that has very limited treatment options,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “This milestone represents significant progress in our collaboration and development program with Ipsen to expand the use of Cabometyx to additional patient populations outside of the currently approved indication.”
Under the terms of the collaboration and license agreement with Ipsen, upon the acceptance of this filing, Exelixis earned a $10 million milestone payment. Due to new revenue recognition standards the company adopted in the first quarter of 2018, Exelixis will not record this amount as revenue but expects the milestone to be paid by Ipsen in the second quarter of this year.
On March 6, 2017, the US Food and Drug Administration (FDA) granted orphan drug designation to cabozantinib for the treatment of advanced HCC. On October 16, 2017, Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended that the trial be stopped for efficacy following review at the second planned interim analysis.
On March 15, 2018, Exelixis announced the completed submission of a supplemental New Drug Application (sNDA) to the FDA for Cabometyx for previously treated advanced HCC based on findings from CELESTIAL. An sNDA is an application to the FDA that, if approved, will allow a drug sponsor to make changes to a previously approved product label, including modifications to the indication.
CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.
Cabometyx tablets are approved in the United States for the treatment of patients with advanced renal cell carcinoma (RCC). Cabometyx tablets are also approved in the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy. Ipsen also submitted to the EMA the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on March 23, 2018, the CHMP provided a positive opinion for Cabometyx for the first-line treatment of intermediate- or poor-risk advanced RCC. 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, including RCC.
Cabometyx is not indicated for previously treated advanced HCC.
marketing authorization from the European Medicines Agency (EMA), the European regulatory authority, for the addition of a new indication for patients with previously treated advanced hepatocellular carcinoma (HCC). The filing is based on results of the global pivotal phase 3 CELESTIAL trial, which met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with advanced HCC who had been previously treated with sorafenib (pre-specified critical p-value = 0.021).
“We are excited by the potential benefit Cabometyx may offer patients in the European Union diagnosed with previously treated advanced hepatocellular carcinoma, a patient community that has very limited treatment options,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “This milestone represents significant progress in our collaboration and development program with Ipsen to expand the use of Cabometyx to additional patient populations outside of the currently approved indication.”
Under the terms of the collaboration and license agreement with Ipsen, upon the acceptance of this filing, Exelixis earned a $10 million milestone payment. Due to new revenue recognition standards the company adopted in the first quarter of 2018, Exelixis will not record this amount as revenue but expects the milestone to be paid by Ipsen in the second quarter of this year.
On March 6, 2017, the US Food and Drug Administration (FDA) granted orphan drug designation to cabozantinib for the treatment of advanced HCC. On October 16, 2017, Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended that the trial be stopped for efficacy following review at the second planned interim analysis.
On March 15, 2018, Exelixis announced the completed submission of a supplemental New Drug Application (sNDA) to the FDA for Cabometyx for previously treated advanced HCC based on findings from CELESTIAL. An sNDA is an application to the FDA that, if approved, will allow a drug sponsor to make changes to a previously approved product label, including modifications to the indication.
CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.
Cabometyx tablets are approved in the United States for the treatment of patients with advanced renal cell carcinoma (RCC). Cabometyx tablets are also approved in the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy. Ipsen also submitted to the EMA the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on March 23, 2018, the CHMP provided a positive opinion for Cabometyx for the first-line treatment of intermediate- or poor-risk advanced RCC. 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, including RCC.
Cabometyx is not indicated for previously treated advanced HCC.