Eisai and Merck (NYSE: MRK) announced on 8/23/18 that the European Commission (EC) has granted a marketing authorization for the oral receptor tyrosine kinase (RTK) inhibitor Lenvima (lenvatinib), as a single agent for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy. Treatment options for this type of liver cancer are limited, and the prognosis is poor. Lenvima is the first new, first-line treatment for advanced or unresectable HCC in a decade to show an overall survival (OS) treatment effect by statistical confirmation of non-inferiority against standard of care.
Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for nearly 750,000 deaths per year globally (69,000 per year in Europe), with over 780,000 cases newly diagnosed each year (71,000 per year in Europe). Hepatocellular carcinoma represents about 90 percent of primary liver cancer cases and due to the underlying nature of the disease, surgery is generally not an option.
“Patients with hepatocellular carcinoma are faced with a cancer that is difficult to treat and has a particularly poor prognosis, with only one systemic first-line treatment option currently available,” said Gary Hendler, Chairman and CEO, Eisai EMEA. “Lenvima is the first new treatment option to be made available in this first-line systemic treatment setting in over a decade and represents an important new therapeutic option for patients. Eisai and Merck are therefore committed to working together to ensure that patients have rapid access to Lenvima across Europe.”
This approval was based on results from REFLECT (Study 304), an open-label, Phase 3 trial where Lenvima demonstrated a treatment effect on OS by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC. Lenvima also demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS) and objective response rate (ORR).
Lenvima was discovered and developed by Eisai. It is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvima inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α (FRS2α) phosphorylation.
Eisai and Merck announced on 8/16/18 that Lenvima had been approved in the US as a first line treatment for patients with unresectable hepatocellular carcinoma