Date: 2018-09-20
Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Cabometyx™
Compound: cabozantinib
Therapeutic area: Cancer - Oncology
Action mechanism:
- tyrosine kinase inhibitor. Cabozantinib is a kinase inhibitor that blocks abnormal kinase proteins involved in the development and growth of medullary cancer cells. Cabozantinib inhibits the activity of tyrosine kinases including MET, AXL and VEGFR-1, -2 and -3. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.
- In February 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan.
Company: Exelixis (USA - CA) Ipsen (France)
Disease: hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib
Latest news:
- • On September 20, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive
opinion recommending a change to the terms of the marketing authorisation for Cabometyx®. The CHMP adopted a new indication as follows: “Cabometyx is indicated as monotherapy for the treatment of hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib.”
- The EMA filing is based on the results of the global placebo-controlled 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 have been previously treated with sorafenib. In July 2018, CELESTIAL phase 3 pivotal trial results were published in the New England Journal of Medicine. CELESTIAL is a randomized, double-blind, placebo-controlled global phase 3 study of cabozantinib versus placebo in patients with advanced HCC who have been previously treated with sorafenib. The study was conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who previously received 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, and 773 patients were ultimately randomized. 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. The primary endpoint for the trial is OS, and secondary endpoints include objective response rate (ORR) and progression-free survival (PFS). Exploratory endpoints include patient-reported outcomes, biomarkers and safety.
- Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events.
- CELESTIAL trial met its primary endpoint, with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared to placebo in patients with advanced HCC. The independent data monitoring committee for the study recommended that the trial should be stopped for efficacy following review of the second planned interim analysis. The safety data in the study were consistent with the established profile of cabozantinib.
- • On May 29, 2018, Exelixis announced that the FDA has accepted for filing the company’s supplemental New Drug Application (sNDA) for Cabometyx® (cabozantinib) tablets as a treatment for patients with previously treated advanced hepatocellular carcinoma (HCC). The FDA has completed its filing review and has determined that the application is sufficiently complete to permit a substantive review. The filing has been assigned a Prescription Drug User Fee Act (PDUFA) action date of January 14, 2019.
- On March 28th, 2018, Ipsen announced that the European Medicines Agency (EMA), the European regulatory authority, has validated the filing of a new application for an additional indication for Cabometyx®, for patients with previously treated advanced hepatocellular carcinoma . The filing is based on the results of the global placebo-controlled phase 3 CELESTIAL trial which met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant improvement and clinically meaningful improvement in median OS compared with placebo in patients with advanced hepatocellular carcinoma who have been previously treated with sorafenib.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization:
Favourable opinion UE:
Favourable opinion USA: 2018-09-20
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
