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News Release

FOR IMMEDIATE RELEASE
June 5, 2017

EISAI TO PRESENT RESULTS OF PHASE III TRIAL OF LENVIMA® (LENVATINIB) AS FIRST-LINE TREATMENT FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA IN ORAL SESSION AT 53RD ASCO ANNUAL MEETING
PRIMARY ENDPOINT ACHIEVED AND STATISTICALLY SIGNIFICANT IMPROVEMENT OF SECONDARY ENDPOINTS COMPARED WITH SORAFENIB

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the results of a Phase III trial (Study 304) of its in-house discovered and developed anticancer agent lenvatinib mesylate (product names: Lenvima® / Kisplyx®, “lenvatinib”) against the comparator sorafenib as first-line treatment for unresectable hepatocellular carcinoma, will be orally presented during the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO), taking place in Chicago, the United States. In this study, lenvatinib was the first agent to demonstrate statistical non-inferiority against sorafenib in the primary endpoint of Overall Survival (OS) and showed statistically significant and clinically meaningful improvements in the secondary endpoints of Progression Free Survival (PFS), Time To Progression (TTP), and Objective Response Rate (ORR), doubling sorafenib's median values and ratios.

According to the results of the study, lenvatinib (13.6 months) met the statistical criteria for non-inferiority in the primary endpoint of median OS compared to sorafenib (12.3 months). (Hazard Ratio [HR] 0.92, 95% Confidence Interval [CI] = 0.79-1.06)
Additionally, lenvatinib showed statistically significant improvements in the three secondary endpoints compared to sorafenib: median PFS (lenvatinib 7.4 months versus sorafenib 3.7 months, HR 0.66, 95% CI = 0.57-0.77, P<0.00001), median TTP (lenvatinib 8.9 months versus sorafenib 3.7 months, HR 0.63, 95% CI = 0.53-0.73, P<0.00001) and ORR (lenvatinib 24% versus sorafenib 9%, P<0.00001).
Furthermore, when overall Quality of Life (QOL) was evaluated based on the EORTC QLQ-C30 questionnaire, it was found that lenvatinib helped to delay deterioration of QOL, such as pain and diarrhea, compared to sorafenib (nominal P-value < 0.05).
In this study, the five most common adverse events observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, weight loss and fatigue, which is consistent with the known side-effect profile of lenvatinib.

Based on the results of this study, Eisai will submit regulatory applications for lenvatinib for the treatment of hepatocellular carcinoma in Japan, the United States, and Europe during the first half of fiscal 2017, and China within fiscal 2017.

Liver cancer is the second leading cause of cancer related deaths and is estimated to be responsible for 750,000 deaths per year globally.1 Additionally, 780,000 cases are newly diagnosed each year, about 80% of which occur in Asian regions, including Japan and China.1 Hepatocellular carcinoma accounts for 85% to 90% of primary liver cancer cases. Early stage hepatocellular carcinoma is treatable by a wide variety of means, including surgery, radiofrequency ablation, ethanol injection, and chemoembolization therapy, but treatment opinions for unresectable hepatocellular carcinoma are limited and the prognosis is very poor, meaning that this is an area of high unmet medical need.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai remains committed to generating scientific evidence aimed at maximizing the value of lenvatinib as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

<Notes to editors>
1.  About lenvatinib mesylate (generic name, “lenvatinib”, product name: Lenvima® / Kisplyx®)

Discovered and developed in-house, lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor proliferation.
Currently, Eisai has obtained approval for lenvatinib as a treatment for refractory thyroid cancer in 50 countries, including the United States, Japan, and in Europe. Additionally, Eisai has obtained approval for lenvatinib in combination with everolimus in the United States, Europe, and other countries, as a treatment for renal cell carcinoma (second-line). In Europe, lenvatinib was launched under the brand name Kisplyx® for this indication.
A Phase III study of lenvatinib in separate combinations with everolimus and pembrolizumab in renal cell carcinoma (first-line) was initiated and is underway. A Phase Ib/II study to investigate the agent in combination with pembrolizumab in select solid tumors (non-small cell lung cancer, renal cell carcinoma, endometrial cancer, urothelial cancer, head and neck cancer, and melanoma) is underway. Additionally, a Phase Ib study of the agent in hepatocellular carcinoma is also underway.

2.  About Study 304

Study 304 is a multicenter, randomized, open-label, global Phase III study comparing the efficacy and safety of lenvatinib versus sorafenib, a standard treatment for advanced hepatocellular carcinoma, as a first-line treatment for patients with unresectable hepatocellular carcinoma. In the study, 954 patients were randomized in a 1:1 ratio to receive lenvatinib 12 mg or 8 mg once a day, depending on baseline body weight (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity.
The primary endpoint of the study was Overall Survival (OS), with the goal of demonstrating non-inferiority. Other factors including Progression Free Survival (PSF), Time To Progression (TTP), Objective Response Rate (ORR) and Quality of Life (QOL) were assessed as secondary endpoints.

3.  About Hepatocellular Carcinoma

Liver cancer is the second-leading cause of cancer deaths, estimated to be responsible for 750,000 deaths per year globally.1 Additionally, 780,000 cases are newly diagnosed each year.1 There is a large regional difference, with about 80% of new cases occurring in Asian regions, including China and Japan. Hepatocellular carcinoma accounts for 85% to 90% of primary liver cancer cases. Hepatocellular carcinoma is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include hepatitis B virus and hepatitis C virus. However, according to a recent investigation, non-B/non-C hepatocellular carcinoma is on the rise. Surgery is the first option for treatment, however, in many cases of recurrence after resection or when the cancer is deemed advanced at diagnosis, surgery is not applicable due to the disease having already metastasized throughout the body, and so it remains a condition with significant unmet medical needs. The only medicine approved for systemic therapy is sorafenib, making this a disease with unmet medical needs.

4.  About EORTC QLQ-C30

A questionnaire developed by the European Organisation for Research and Treatment of Cancer (EORTC) which is widely used in the field of oncology to assess the quality of life of cancer patients.

1 GLOBOCAN2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/