• Lenvima is the first new systemic therapy approved for the first-line treatment of unresectable HCC in China in ten years
• In China, there are approximately 395,000 new cases of liver cancer and 380,000 deaths per year

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Merck (NYSE: MRK) announced on 9/5/18 that the China National Medical Products Administration (NMPA) approved the kinase inhibitor Lenvima (lenvatinib) as a single agent for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy. In China, the application of Lenvima was submitted in October 2017 and was designated for Priority Review by the NMPA due to Lenvima's significant clinical benefit compared to existing treatments, leading to approval in approximately 10 months. This approval marks the first for Lenvima in China, where the incidence of HCC is high, and the first new systemic therapy approved for the first-line treatment of unresectable HCC in China in ten years.

“Over the past decade, there have been limited treatment options available for patients with unresectable HCC,” said Dr. Takashi Owa, Vice President and Chief Medicine Creation Officer, Oncology Business Group, Eisai. “We are pleased to be able to deliver Lenvima to HCC patients in China, and we are thankful for the collaborative efforts by regulatory and government authorities, as well as the patients and physicians who participated in the clinical studies and made this approval possible.”

The approval was based on results from the REFLECT study (Study 304), an open-label, Phase 3 trial where Lenvima demonstrated a treatment effect on overall survival (OS) by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC; patients randomized to the Lenvima arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. Lenvima demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR). In a subpopulation analysis of 288 patients in the study from the greater Chinese region (mainland China, Hong Kong and Taiwan), Lenvima demonstrated efficacy based on non-inferiority of OS compared to sorafenib, with improvements also observed in PFS, TTP and ORR. Approximately 80% of patients in the subpopulation were living with HCC resulting from chronic hepatitis B virus (HBV), which has high unmet medical need. For these patients, Lenvima demonstrated non-inferiority based on OS compared with sorafenib, thereby demonstrating the effect of Lenvima in patients with HCC resulting from HBV.

Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for approximately 750,000 deaths per year globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80% of which occur in Asian regions. Specifically, in China, there are approximately 395,000 new cases and 380,000 deaths per year, accounting for approximately 50% of cases worldwide. HCC accounts for 85% to 90% of primary liver cancer cases. Unresectable HCC, for which treatment options are limited, is extremely difficult to treat, and the development of new treatments is necessary.

Lenvima, discovered and developed by Eisai, 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.