Ipsen announced that the Committee for Medicinal Products for Human Use (CHMP), the European Medicines Agency (EMA), provided a positive opinion for Cabometyx® (cabozantinib) as a monotherapy for the treatment of hepatocellular carcinoma (HCC) in adults who have been previously treated with sorafenib.

The CHMP positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU).

Alexandre Lebeaut, MD, Executive Vice President, R&D, and Chief Scientific Officer, Ipsen, said: "The global burden of liver cancer is increasing and despite the recent introduction of new agents, it remains the second leading cause of cancer mortality worldwide."

Hepatocellular carcinoma

"Following today's positive CHMP opinion and if approved by the European Commission, Cabometyx® as monotherapy will give patients with HCC a much-needed new oral therapeutic option," said Lebeaut.

At the second planned interim analysis, the trial showed significantly longer overall survival with cabozantinib than with placebo. Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005).

Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009).

Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group and 36% in the placebo group. The most common high-grade events were palmar–plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).

Dr. Lorenza Rimassa, Medical Oncology Unit, Humanitas Cancer Center, Milan, said: "The medical community is pleased that the CHMP has given a positive opinion to Cabometyx® for previously-treated patients with hepatocellular carcinoma."

"The fact that Cabometyx® demonstrated clinically significant benefits in both overall survival and progression-free survival in phase 3 CELESTIAL study confirms the value it brings to this difficult treatment landscape," said Rimassa.

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. Today's CHMP positive opinion follows two earlier European Commission approvals for Cabometyx® in renal cell carcinoma (RCC). 

Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. The rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group.