Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced the first results for metastatic endometrial carcinoma obtained from a Phase Ib/II study (Study 111) of its in-house developed multi-kinase inhibitor lenvatinib mesylate (product names: Lenvima® / Kisplyx®, “lenvatinib”) in combination with the MSD (known as Merck & Co., Inc, Kenilworth, NJ, USA in the United States and Canada) anti-PD-1 antibody pembrolizumab (brand name: KEYTRUDA®^*), during a presentation at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO), taking place in Chicago, the United States. The two companies are collaborating to develop this combination therapy. Study 111 is being conducted to evaluate the activity of the lenvatinib/pembrolizumab combination in select solid tumors.

The presentation covers an analysis of a combined total of 23 endometrial carcinoma patients over both the Phase Ib and Phase II parts of the study, who had previously undergone at least one chemotherapy regimen. After being treated with a combination of lenvatinib and pembrolizumab, the results of the analysis showed the primary endpoint of objective response rate was 52.2% (95% Confidence Interval [CI] = 30.6 – 73.2) based on an independent radiologic review (IRR) and 47.8% (95% CI: 26.8 – 69.4) by investigator review.
The secondary endpoints of clinical benefit rate^** were 65.2% (95% CI: 42.7 – 83.6) by IRR and 73.9% (95% CI: 51.6 – 89.8) by investigator review. Disease control rate^***were 91.3% (95% CI: 72.0 – 98.9) by IRR and 95.7% (95% CI: 78.1 – 99.9) by investigator review. Median progression-free survival was 9.7 months (95% CI: 4.2 – NE) based on investigator assessment and was not reached by IRR. Median duration of response was not reached at the time of analysis.
Anti-PD-1 antibodies are generally more effective in patients with a high frequency of microsatellite instability (MSI), a biomarker that results in dysfunctional DNA mismatch repair, and less effective in other patients. However, in this study, the combination therapy resulted in tumor response regardless of the state of their MSI.
The most frequently observed adverse events for the combination regimen (Top 5) were hypertension, fatigue, arthralgia, diarrhea, and nausea.

Endometrial cancer is the sixth most common cancer in women worldwide, with 320,000 new cases diagnosed in 2012. In the United States, it is estimated that approximately 60,000 women will be newly diagnosed with endometrial cancer, and approximately 10,000 women will die from the disease in 2017. Therefore, this remains a disease with significant unmet medical needs and necessitates the development of new treatments.

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.

*   KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, NJ, USA.
**  Clinical benefit rate: Percentage of patients who had complete response, partial response, or maintained disease stability for 23 weeks or longer.
*** Disease control rate: Percentage of patients who had complete response, partial response, or maintained disease stability for 5 weeks or longer.

On April 19, 2017, Eisai China Inc. (hereinafter referred to as: Eisai (China)) was invited to attend the “Health to Countryside” activity held in Yudu County, Jiangxi Province by the National Committee for Education, Science, Culture, Health and Sports of Chinese People’s Political Consultative Conference (CPPCC), and donated medicines worth RMB540,000 yuan to the local hospitals. According to the statistics, Eisai (China), practicing the philosophy of hhc (human health care) all along, donated medicines worth RMB450,000, RMB490,000, RMB500,000 and RMB540,000 respectively to this activity from the year 2014 to 2017, with the total worth of medicines reaching up to RMB1.98 million yuan.

Eisai (China) donated medicines worth RMB540, 000 yuan to the “Health to Countryside” activity.

The “Health to Countryside” is an important and traditional activity annually organized by the National Committee for Education, Science, Culture, Health and Sports of CPPCC, implementing CPPCC’s articles of association. This activity not only delivers doctors, medicines, concepts, technologies and management to the grassroots, but also narrows the distance between the committee members, the experts and the masses. It coincides with what Eisai (China) has always been pursuing – the hhc philosophy. Eisai (China) advocates that every year every Eisai staff shall spend about 1% of their working hours on practicing hhc with patients, for the simple fact that only with the empathy of patients’ feelings and pains can Eisai provide better services as well as products in need to earn the trust from patients and their families. Eisai (China) will, led by its President Mr. Kaneko Norio and the General Manager Ms. Feng Yanhui (Fendy Feng), continuously contribute to the medical and health services in poor areas by donating medicines to the “Health to Countryside” activity.

The donation Certificate granted to Eisai China Inc.

On the donation ceremony, the Chinese Hospital Association’s President Mr. Huang Jiefu, the Deputy Secretary of CPC Yudu County Committee, the Director of Yudu County Health and Family Planning Commission and other leaders made their speeches. Mr. Xue Xiaolin, the Executive Vice President of Chinese Hospital Association, signed an agreement of donation with Yudu County Health and Family Planning Commission. After the ceremony, President Huang Jiefu, Executive Vice President Xue Xiaolin and other leaders praised Eisai (China)’s years of participation in this activity and expressed their high recognition for Eisai’s hhc philosophy. Finally, President Huang Jiefu said that the “Health to Countryside” activity would continue and more medical and health institutions would be welcomed to join the team for more contributions to the development of medical and health services.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has presented the latest research data regarding a mechanism of action that led to increased anti-tumor activity in mouse models which had been dosed with a combination of the in-house developed anticancer agent lenvatinib mesylate (lenvatinib) and an anti-mouse PD-1 antibody, at the American Association for Cancer Research (AACR) 108th Annual Meeting.

The results presented at the AACR meeting showed that when syngeneic model mice inoculated with mouse liver cancer, melanoma or colon cancer cell lines were dosed with a combination of lenvatinib (10 mg/kg, once daily) and an anti-mouse PD-1 antibody (500 g/mouse, twice a week), lenvatinib alone or an anti-mouse PD-1 antibody alone, a substantial inhibitory effect on tumor growth was observed in mice that had been dosed with the combination therapy compared to the single treatments.
Additionally, an increased number of mice in the combination therapy group showed Complete Response (CR) of tumor compared to the single treatment group. Specifically, in the combination therapy group, 7 out of 30 mice showed CR (colon cancer models: 2/10, melanoma models: 2/10, liver cancer models: 3/10), whereas in each single treatment group, 1 out of 30 mice showed CR (colon cancer models: 1/10, melanoma models: 0/10, liver cancer models: 0/10).

Furthermore, in the liver cancer mouse model, even when identical cancer cell lines were re-inoculated into mice with complete tumor remission, no in vivo growth was observed.

RNA analysis of the cancer tissue and other tests confirmed a reduction in immunosuppressive tumor associated macrophages, a reduction in immunosuppressive signal receptors, and an increase in the ratio of memory T cells in model mice dosed with lenvatinib.

This non-clinical research suggested synergistic anti-tumor activity when combining lenvatinib with an anti-mouse PD-1 antibody in the mouse models, based on an immunostimulatory response due to the reduction in tumor associated macrophages and the enhancement of the ratio of memory T cells by lenvatnib.

Eisai has positioned oncology as a key therapeutic area of focus and remains committed to providing further evidence for 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.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai” ) announced today that the German Federal Joint Committee (G-BA) has confirmed the additional benefit of in-house developed anticancer agent Kisplyx^® (lenvatinib mesylate) in combination with everolimus for the treatment of advanced renal cell carcinoma (RCC) compared to everolimus alone in its assessment for insurance reimbursement. Based on this additional benefit assessment, price negotiations with the Head Association of German Sick Funds (GKV-SV) will be conducted, and a reimbursement price has to be agreed.

The G-BA’s assessment was based on a Phase II clinical study (Study 205) that evaluated the safety and efficacy of Kisplyx in combination with everolimus in patients with unresectable advanced or metastatic RCC following one prior vascular endothelial growth factor (VEGF) targeted therapy. From the results of the study, the Kisplyx plus everolimus group demonstrated a significant extension in the study’s primary endpoint of progression free survival (PFS) compared to the everolimus alone group. Furthermore, the Kisplyx plus everolimus group demonstrated an extension in median overall survival (OS) compared to the everolimus alone group.
The most common treatment-emergent adverse events (TEAEs) reported in the Kisplyx plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) were diarrhea, hypertension and fatigue

The number of patients with renal cancer is estimated to be approximately 115,000 in Europe in 2012. Renal cell carcinoma comprises more than 90% of all malignancies of the kidney, and originates from malignant cells in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people over 55 years of age is rising, and it is more likely to affect men than women. For advanced or metastatic RCC that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy. However, with low 5-year survival rates, RCC remains a disease with a significant unmet medical need.

In Europe, lenvatinib mesylate has been designated as an orphan drug for thyroid cancer and is marketed as Lenvima^® for this indication.

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 expanding access to Kisplyx and maximizing value of the drug 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.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito) announced today that, in association with its U.S. pharmaceutical subsidiary Eisai Inc. (collectively, “Eisai”), it has reached an agreement with Arena Pharmaceuticals, Inc. (Headquarters: California, United States, President and CEO: Amit D. Munshi) to revise the November 2013 marketing and supply agreement it concluded with Arena’s wholly owned subsidiary, Arena Pharmaceuticals GmbH (collectively, “Arena”), for the chronic weight management treatment lorcaserin hydrochloride (generic name, U.S. brand name: BELVIQ® / BELVIQ XR®, “BELVIQ”). Under the new agreement, Eisai acquires all of Arena’s rights to develop and market BELVIQ.

Under the latest agreement, Eisai becomes solely responsible for all decision-making and implementation related to global development and submissions for regulatory approvals, as well as global marketing for BELVIQ. The previously negotiated financial terms such as purchase price based on net sales and regulatory and sales milestones to Arena have also been reduced and modified. In addition, a technology transfer will take place to allow Eisai to participate in the manufacture of BELVIQ. Eisai will also assume Arena’s exclusive distribution agreements with third-parties to develop and market BELVIQ in South Korea, Chinese Taiwan and Israel. Eisai will now serve as the third parties’ exclusive supplier and receive income in the form of payment for the supply of product to the distributors.

BELVIQ was approved by the U.S. Food and Drug Administration (FDA) in 2012 as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related co-morbid condition, and has been available to patients in the United States since June 2013. In addition, BELVIQ has been made available in South Korea via a third-party distributor contracted by Arena from 2015. In 2016, lorcaserin was approved in both Brazil and Mexico, and will be launched in Mexico under the brand name VENESPRI®. In addition, BELVIQ XR, a once-daily formulation of lorcaserin was approved in the United States in 2016.

By seeking to further the development of BELVIQ and to expand its availability to more patients, Eisai anticipates that the new agreement will give it greater freedom in its development and submission strategy, support its goal of making contributions to address unmet medical needs in the clinical management of obesity and increase the benefits for patients and their families worldwide.