Ipsen Announces EMA Validation of Filing of a New Application for Additional Indication for Cabometyx®, for Patients with Previously Treated Advanced Hepatocellular Carcinoma (HCC)

 Ipsen (Euronext: IPN; ADR: IPSEY) today 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 (HCC).

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.

Alexandre Lebeaut, MD, Executive Vice-President, R&D, Chief Scientific Officer, Ipsen, said:

"This milestone is an important step forward for the cabozantinib ongoing development program across solid tumors, with the potential, if approved, to provide patients with advanced HCC - which is still an unmet medical need - with a new oral systemic treatment."

About CELESTIAL

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 and progression-free survival. 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 of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in median OS compared to placebo in patients with advanced hepatocellular carcinoma (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.

About HCC

Hepatocellular Carcinoma (HCC) is the most common form of liver cancer in adults.¹The disease originates in cells called hepatocytes found in the liver. With approximately 800’000 new cases diagnosed each year, HCC is the sixth most common cancer and the second-leading cause of cancer deaths worldwide.^2,3According to the GLOBOCAN data, it is estimated that across the European Union (EU-28) nearly 60’000 new patients will be diagnosed with liver cancer in 2020.⁴ Without treatment, patients with the disease in advanced stage usually survive between 4 and 8 months.⁵

About CABOMETYX^® (cabozantinib)

Cabometyx^® is an oral small molecule inhibitor of receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

In February of 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. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada. On April 25, 2016, the FDA approved Cabometyx^® tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy and on September 9, 2016, the European Commission approved Cabometyx^® tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx^® is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On September 8, 2017, Ipsen announced that the EMA validated the application for cabozantinib as a treatment for first-line advanced RCC in the European Union; on March 22 2018, the CHMP issued a positive opinion for this indication.

On December 19, 2017, Exelixis received approval from the FDA for Cabometyx^® for the expanded indication of treatment of advanced RCC.

Cabozantinib is not approved for the treatment of advanced hepatocellular carcinoma.

About Ipsen

Ipsen is a global specialty-driven biopharmaceutical group focused on innovation and specialty care. The group develops and commercializes innovative medicines in three key therapeutic areas - Oncology, Neurosciences and Rare Diseases. Its commitment to oncology is exemplified through its growing portfolio of key therapies for prostate cancer, neuroendocrine tumors, renal cell carcinoma and pancreatic cancer. Ipsen also has a well-established Consumer Healthcare business. With total sales over €1.9 billion in 2017, Ipsen sells more than 20 drugs in over 115 countries, with a direct commercial presence in more than 30 countries. Ipsen's R&D is focused on its innovative and differentiated technological platforms located in the heart of the leading biotechnological and life sciences hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US). The Group has about 5,400 employees worldwide. Ipsen is listed in Paris (Euronext: IPN) and in the United States through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY)

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