Eisai Co., Ltd. (Headquarters: Bunkyo-ku, Tokyo, CEO: Haruo Naito, “Eisai”) and Ono Pharmaceutical Co., Ltd. (Headquarters: Chuo-ku, Osaka, Representative Director and President: Gyo Sagara, “Ono”) have announced that they have entered into a collaboration agreement to jointly develop the combination therapy of Eisai¡®s multi-kinase inhibitor, Lenvima? (lenvatinib mesylate) and Ono¡¯s human anti-human PD-1 (programmed cell death-1) monoclonal antibody, Opdivo? (nivolumab) for the treatment of hepatocellular carcinoma (HCC).

Based on this agreement, Eisai and Ono will swiftly implement a Phase Ib clinical trial in Japan to investigate the safety, tolerability, and efficacy of the combination of Lenvima and Opdivo in patients with HCC. Details relating to the financial and other conditions of this agreement are confidential.

Liver cancer is the second most common cause of cancer related deaths, with an estimated 750,000 deaths per year globally. Additionally, 780,000 cases are newly diagnosed each year, about 80% of which occur in Asian regions, including Japan and China. HCC accounts for approximately 85% to 90% of liver cancer cases. It is estimated that there are approximately 42,000 HCC patients in Japan, with 26,000 deaths per year. Treatment options for unresectable HCC are limited and the prognosis is very poor, so this remains an area with high unmet medical needs.
Eisai submitted an application for an additional indication of Lenvima for the treatment of HCC in Japan in June 2017. Ono is currently conducting a Phase III clinical trial of Opdivo for the treatment of HCC in Japan.

Dr. Takashi Owa, Vice President, Chief Medicine Creation Officer, Oncology Business Group, Eisai, commented, “Our non-clinical research has demonstrated synergistic antitumor activities in the Lenvima and anti-PD1 antibody combination, which are considered to be a result of an immunostimulatory response through a reduction in immunosuppressive tumor-associated macrophages and an increase in cytotoxic T lymphocytes by Lenvima. Through the development of a combination therapy that has the potential to produce synergistic effects between Lenvima and nivolumab, both drugs of Japanese origin, we anticipate being able to further contribute to addressing the high unmet medical needs of HCC patients and their families and improving their benefits.”

Hiroshi Awata, Vice President Executive Officer / Executive Director, Clinical Development, Ono, commented, “We have been actively engaged in the development of Opdivo not only in monotherapy, but combination therapies with other agents. As we believe that the combination therapy may exert more excellent therapeutic efficacy compared to the monotherapy, we are very pleased to pursue the potential for developing the combination therapy of Opdivo with lenvatinib. We expect that the combination therapy with Opdivo and lenvatinib will be a new treatment option for the patients with hepatocellular carcinoma.”