INTERIM ANALYSIS OF PHASE Ib/II STUDY OF ERIBULIN AND PEMBROLIZUMAB COMBINATION REGIMEN IN METASTATIC TRIPLE NEGATIVE BREAST CANCER PRESENTED AT SAN ANTONIO BREAST CANCER SYMPOSIUM

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the results of an interim analysis of a Phase Ib/II clinical study (Study 218) of its in-house discovered and developed anticancer agent eribulin mesylate (halichondrin class microtubule dynamics inhibitor, product name: Halaven®, “eribulin”) in combination with the anti-PD-1 antibody pembrolizumab developed by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the U.S. and Canada), in patients with metastatic triple-negative breast cancer have been presented at the 39th Annual San Antonio Breast Cancer Symposium held from December 6 to 10, 2016. Development of this combination regimen is being conducted jointly under the cooperation of both companies.

Study 218 is a Phase Ib/II clinical study which examined the activity and safety of eribulin in combination with pembrolizumab in 95 patients with metastatic triple-negative breast cancer previously treated with 0 – 2 lines of chemotherapy in the metastatic setting. The primary objective of the Phase Ib part was safety and tolerability, and the primary objective of the Phase II part was objective response rate (ORR).

This presentation reported on the results of an interim analysis of 39 evaluable patients out of the 89 patients enrolled in the study as of July 2016. Eribulin (1.4 mg/m²intravenously on Day 1 and Day 8) and pembrolizumab (200 mg intravenously on Day 1) were administered to patients over 21 day cycles. From the results of the study, ORR was 33.3% (1 patient experienced a complete response and 12 patients experienced a partial response). In addition, the ORR was similar between PD-L1 positive and negative cohorts.

In this study, the most common treatment-emergent adverse events (incidence greater than or equal to 35%) in patients treated with the combination regimen were fatigue, nausea, peripheral neuropathy, neutropenia and alopecia, with Grade 3 or higher Treatment-Emergent Adverse Events (TEAEs) observed in 66.7% of patients. The most common Grade 3 or higher TEAEs (incidence greater than or equal to 7%) observed were neutropenia (30.8%) and fatigue (7.7%).

Eribulin is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Recent non-clinical studies showed that eribulin is associated with increased vascular perfusion and permeability in tumor cores.¹ Eribulin promotes the epithelial state and decreases the capacity of breast cancer cells to migrate and invade.² It was first approved for use in the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved for use in the treatment of patients with breast cancer in over 60 countries including Japan and countries in Europe, the Americas and Asia.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. As exemplified by this combination regimen, Eisai remains committed to providing further clinical evidence for eribulin aimed at 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 PRESENTS LATEST DATA ON BACE INHIBITOR ELENBECESTAT（E2609）AT 9TH CLINICAL TRIALS ON ALZHEIMER’S DISEASE

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has presented the latest two clinical trials (Study 202 and Study 006) data on its in-house discovered oral BACE (beta amyloid cleaving enzyme ) inhibitor elenbecestat (development code: E2609) at the 9th Clinical Trials on Alzheimer’s Disease (CTAD 2016) held from December 8 to 10 in San Diego, the United States.

Study 202 is a multicenter, randomized, double-blind, placebo-controlled parallel-group phase II clinical study to evaluate the safety of elenbecestat and the change from baseline in cerebrospinal fluid (CSF) amyloid beta Aβ(1-x)* level in patients with mild cognitive impairment (MCI) due to Alzheimer’s disease or mild to moderate dementia due to Alzheimer’s disease with confirmed accumulation of amyloid beta (Aβ) by PET (positron emission tomography) screening. Patients are administered 5, 15 or 50 mg of elenbecestat daily. The change in Aβ(1-x) level is evaluated by analyzing the concentrations of Aβ(1-x) in plasma and CSF before and after elenbecestat administration. The presentation highlighted the results from a preliminary analysis of pharmacokinetic and pharmacodynamics data of Study 202 at the CTAD 2016 (poster presentation number: P3-28).
In Study 202, the pharmacokinetic profile of elenbecestat was similar to the results obtained from Phase I studies in healthy volunteers. A correlation between plasma concentration of elenbecestat and the decrease in CSF Aβ(1-x) was observed, which overlapped with exposure-response models combining data from this study and Phase I clinical study data (figure 1).
* Aβ(1-x) refers to Aβ peptides of all lengths

Furthermore, a dose-response model was established to explain the relationship between dosage of elenbecestat and the decrease in CSF Aβ(1-x) using the same dataset. This model was able to describe the decrease in CSF Aβ(1-x) in Study 202 well. The predicted median reduction in CSF Aβ(1-x) at 50 mg/day dose of elenbecestat was 70% (figure 2). Based upon these results, a global Phase III clinical study (MISSION AD) is currently underway to confirm efficacy and safety of elenbecestat at a dosage of 50 mg/day.

Study 006 was a bridging study (Phase I clinical study) of elenbecestat to investigate similarity of the pharmacokinetics, pharmacodynamics and safety profiles between Japanese and white healthy subjects (poster presentation number: P3-27). The study was conducted as a randomized, double-blind, placebo-controlled study. Single oral doses of 5, 50 or 200 mg/day of elenbecestat were administered in healthy adult Japanese and 50 mg/day of elenbecestat in white subjects, respectively.
From the results of the study, a dose-dependent decrease in plasma Aβ(1-x) level was observed in Japanese subjects. Pharmacokinetic and pharmacodynamics profiles were similar between Japanese and white subjects. There were no specific racial differences in safety findings.

Discovered in-house by Eisai, elenbecestat is an investigational oral BACE inhibitor currently being investigated in a Phase III clinical study for Alzheimer’s disease. By inhibiting BACE, a key enzyme in the production of Aβ peptides, elenbecestat decreases the formation of these peptides which can aggregate into toxic oligomers and protofibrils and eventually form amyloid plaques in the brain. It is believed that decreasing the formation of these plaques may potentially slow disease progression. Elenbecestat is being jointly developed by Eisai and Biogen Inc. (Headquarters: Massachusetts, United States, CEO: George A. Scangos, “Biogen”). In addition, the U.S. Food and Drug Administration has granted Fast Track designation for the development of elenbecestat.

Eisai considers dementia a therapeutic area of focus and is committed to new drug such as elenbecestat development in this field. Eisai is striving to bringing promising therapies to patients worldwide as early as possible.

EISAI TO PRESENT LATEST DATA ON ERIBULIN AT 39TH ANNUAL SAN ANTONIO BREAST CANCER SYMPOSIUM

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that a series of abstracts highlighting the latest clinical data on its in-house developed halichondrin class microtubule dynamics inhibitor eribulin mesylate (product name: Halaven®, “eribulin”) will be presented at the San Antonio Breast Cancer Symposium (SABCS2016) taking place in San Antonio, the United States, from December 6 to 10.

Three abstract poster presentations (including outcome research data) are to be given at the meeting, with the main presentation featuring the results of an interim analysis of a Phase Ib/II trial (Study 218) of eribulin in combination with the immune checkpoint inhibitor pembrolizumab in patients with metastatic triple-negative breast cancer.

Eisai positions oncology as a key franchise area and is aiming to discover revolutionary new medicines with the potential to cure cancer. The company will continue to create innovation in the development of new drugs based on cutting-edge cancer research, and in doing so seeks to make further contributions to address the diversified needs of, and to increase the benefits provided to, patients and their families as well as to healthcare providers.

EISAI TO PRESENT LATEST DATA ON PERAMPANEL AND RUFINAMIDE AT 70TH AMERICAN EPILEPSY SOCIETY ANNUAL MEETING

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the latest data on its antiepileptic drugs (AED) perampanel (product name: Fycompa®) and rufinamide (product name: Inovelon®, U.S. product name: BANZEL®) will be presented at the 70th American Epilepsy Society (AES) Annual Meeting to be held from December 2 to 6 in Houston in the United States.

For this year’s AES meeting, poster presentations will be given on eight abstracts for perampanel which include the results of Phase II trials (Study 231, Study 233) of adjunctive perampanel in Japanese patients with refractory partial-onset seizures. Regarding rufinamide, a poster presentation will be given on the safety and cognitive development effects of adjunctive rufinamide in pediatric subjects with inadequately controlled Lennox-Gastaut Syndrome (LGS) from the final results of Study 303. Along with three poster presentations on health economics and outcome research, a total of 12 poster presentations will be given.

Perampanel is a first-in-class AED discovered and developed by Eisai. With epileptic seizures being mediated by the neurotransmitter glutamate, the agent is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic AMPA receptors. The agent is currently approved in more than 50 countries and territories as an adjunctive treatment of partial-onset seizures (with or without secondarily generalized seizures) in adult and adolescent patients with epilepsy 12 years of age and older. In addition, perampanel is approved in more than 40 countries as an adjunctive treatment of primary generalized tonic-clonic (PGTC) seizures in patients with epilepsy 12 years of age and older.

Furthermore, Eisai has submitted a supplemental application to the U.S. Food and Drug Administration for a partial label change for perampanel as monotherapy for treatment of partial-onset seizures in patients with epilepsy 12 years of age and older.

Rufinamide is believed to exert its antiepileptic effects by regulating activity of voltage-gated sodium channels in the brain involved in the overexcitement of neurons that potentially causes seizures, so as to prolong their inactive state. The agent is approved as an adjunctive therapy to other AEDs in the treatment of seizures associated with LGS in Europe and the United States. In Japan, the agent is approved as an adjunctive therapy to other AEDs in the treatment of tonic and atonic seizures associated with LGS when therapy with other AEDs is considered inadequate. Rufinamide is currently approved in more than 30 countries worldwide.

Eisai considers epilepsy a therapeutic area of focus and by providing multiple treatment options in addition to perampanel and rufinamide as part of an extensive epilepsy product portfolio, Eisai seeks to make continued contributions to address the diverse needs of, as well as increasing the benefits provided to, patients with epilepsy and their families.

STATEMENT REGARDING THE RESULTS OF THE ACCESS TO MEDICINE INDEX 2016

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that Eisai has been highly commended for its initiatives to promote access to medicines and ranked 11th among the world’s leading pharmaceutical companies in the Access to Medicine Index (ATM Index) 2016.

This Index is compiled by the Access to Medicine Foundation (the Foundation), an international non-profit organization dedicated to improving access to medicine for patients in need. Based on publicly disclosed information and individual surveys, the ATM Index independently evaluates companies’ efforts to improve access to medicine for diseases and countries designated by the Index to rank the world’s top 20 pharmaceutical companies leading in initiatives for access to medicine issues in developing and emerging countries. The ATM Index has been published by the Foundation every two years since 2008.

Eisai performed above the Index average in the following four technical areas set by the Foundation: general access to medicine management, market influence & compliance, research & development, as well as product donations.
In the ATM Index 2016 report, Eisai’s commitment to eliminating lymphatic filariasis, a neglected tropical disease, by providing 2.2 billion diethylcarbamazine citrate (DEC) tablets free of charge to endemic countries in collaboration with the World Health Organization (WHO) for a seven year period starting from 2013, was highly commended. In addition, the Foundation highlighted as best practices Eisai’s strategies for using partnerships to accelerate research and development of new treatments for conditions including neglected tropical diseases (NTDs), malaria and tuberculosis, as well as its initiatives to create patient value with all employees around the world using 1% of their total business hours to interact with patients.

Eisai is establishing proactive partnerships with various stakeholders including governments, international organizations and other non-profit private sector organizations to improve access to medicines worldwide under its human health care (hhc) philosophy. Together with accelerating the development of new medicines for infectious diseases endemic in developing and emerging countries through these partnerships, the Eisai Group is committed to additional long-term sustainable strategies including raising disease awareness locally and implementing price setting models that take income levels into account for greater access to medicine worldwide.

Please click the following link for details of the ATM Index 2016 results:
http://www.atmindex.org

U.K. NICE RECOMMENDS ANTICANCER AGENT HALAVEN® AS TREATMENT FOR ADVANCED BREAST CANCER

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its in-house developed anticancer agent Halaven® (eribulin mesylate, “eribulin”) has been recommended by the U.K. National Institute for Health and Clinical Excellence (NICE) as a treatment for patients with locally advanced or metastatic breast cancer who have received at least two chemotherapeutic regimens for advanced disease (prior therapy may have included an anthracycline or a taxane, and capecitabine) in NICE’s Final Appraisal Determination (FAD). Eribulin is the first breast cancer treatment to be recommended by NICE since 2007.
Following the issue of the FAD by NICE, eribulin will be eligible for reimbursement for this indication via the National Health Service in England (NHS England).

The Appraisal Committee considered that the models suggest Eribulin offers a mean overall survival benefit of more than 3 months. According to the FAD, “In light of the short life expectancy at this stage of breast cancer, the committee considered this overall survival benefit to be substantial. The committee concluded that eribulin met the end-of-life criteria objectively and robustly and that it can be considered a life-extending, end-of-life treatment.”

Eribulin was approved in Europe in March 2011 as a treatment for patients with locally advanced or metastatic breast cancer who have received at least two chemotherapeutic regimens for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. The agent was launched in the U.K. in April 2011. Furthermore, eribulin was approved in June 2014 for an expanded indication to include patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease (prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments).

Eisai regards oncology as a key therapeutic area and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai remains committed to providing further clinical evidence and expanding patient access for eribulin, and by maximizing the value of the drug, seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

CEO Naito Selected among The Best-Performing CEOs in the World by Harvard Business Review

Harvard Business Review has just announced The Best-Performing CEOs in the World, in which CEO Haruo Naito was ranked 87th. Among Japanese companies, only three other CEOs made the list, including Nidec’s Shigenobu Nagamori (42nd), FAST RETAILING’s Tadashi Yanai (46th) and Softbank’s Masayoshi Son (73rd).

From the pharmaceutical industry, only Novo Nordisk’s Lars Rebien Sørensen (1st), Biogen’s George Scangos (21st) and Regeneron Pharmaceuticals’ Leonard Schliefer (67th) made the list, making CEO Naito the only one selected from the Japanese pharmaceutical industry.

Please refer to the following link for further details on the announcement.
https://hbr.org/2016/11/the-best-performing-ceos-in-the-world

This CEO ranking was based on companies in the S&P Global 1200, from 895 CEO’s of 886 companies in 32 countries. The final ranking is calculated based on a financial element measured by shareholder returns and change in market capitalization since becoming CEO of the company as well as a non-financial element assessing ESG (environment, social and governance) initiatives.

EISAI TO OFFICIALLY LAUNCH “CHOCOLA BB® RICH CERAMIDE” IN STORES JAPAN

EISAI TO OFFICIALLY LAUNCH “CHOCOLA BB® RICH CERAMIDE”

IN STORES NATIONWIDE

JAPAN’S FIRST FOOD WITH FUNCTION CLAIMS DRINK CONTAINING CERAMIDE

-“DRINK” TO COUNTER DRY SKIN –

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it will launch its first food with function claims Chocola BB® Rich Ceramide (Notification number: B60) in drugstores, pharmacies and convenience stores throughout Japan on Monday, October 17. The product is Japan’s first drink that is a type of food with function claims containing glucosylceramide derived from rice.

Ceramide is a component of the stratum corneum of the epidermis layer of human skin. Normally, ceramide fills the spaces between cells in the corneum of the skin, and plays a role in restraining the loss of moisture to the outside as well as protecting the skin from external stimuli such as ultraviolet rays. Therefore, a lack of ceramide advances transpiration of skin moisture, potentially leading to dryness in the skin. Since ceramide levels decline with age, it is important to appropriate replenish ceramide to counter dryness.

Containing glucosylceramide as its active component to make it harder for moisture to escape from the skin, Chocola BB Rich Ceramide is a product that you can drink to counter dry skin. Furthermore, in addition to ceramide, the drink also contains collagen and hyaluronic acid which are known for their beauty properties, and is recommended for people who are highly beauty conscious. Chocola BB Rich Ceramide has a delicious, easy to drink pear flavor, is low in calories (8.2 kcal), and with zero caffeine, can be safely consumed before sleep.

Chocola BB Rich Ceramide is now available nationwide through a wide range of retail outlets including drug stores, pharmacies, convenience stores and Eisai’s internet retailing site.

Centered around the signature OTC product Chocola BB® Plus® (Third-class OTC drug) for the relief of skin trouble, acne and mouth ulcers, Eisai has been expanding the Chocola BB brand to suit the needs and lifestyles of its customers such as Chocola BB® Royal 2 (quasi-drug), a nutritional drink for invigoration when physically fatigued, Chocola BB® Joma, a soft drink that contains vitamin B6 (Food with Nutrient Function Claims), and Chocola BB® Mouth Ulcer Repair Shot (Third-class OTC drug), an oral care spray launched in August.

Through the Chocola BB brand, Eisai will continue to respond to the diverse needs of female consumers and support an ever-growing number of people to achieve health and beauty in their everyday lives.

BELVIQ XR® – A NEW ONCE-DAILY FORMULATION OF BELVIQ® FOR CHRONIC WEIGHT MANAGEMENT NOW AVAILABLE IN THE UNITED STATES

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its U.S. subsidiary Eisai Inc. has launched BELVIQ XR® 20mg tablets, a new once-daily formulation of BELVIQ® (generic name: lorcaserin hydrochloride) for chronic weight management in the United States.

BELVIQ XR is an extended release formulation proven to be slowly absorbed in the body and to last throughout the day. The availability of once-daily BELVIQ XR (20mg) in a single tablet provides patients with another dosing option in addition to the conventional twice-daily BELVIQ (10mg).

Approval for twice-daily BELVIQ was obtained in the United States 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 from the U.S. Food and Drug Administration (FDA) in 2012 by Arena Pharmaceuticals, Inc. (Headquarters: California, United States, President and CEO: Amit D. Munshi, “Arena”), whom Eisai and Eisai Inc. have an exclusive licensing agreement with to commercialize lorcaserin hydrochloride, and was launched in June 2013. Once-daily BELVIQ XR was approved with the same indication by the FDA in July 2016.

“Eisai is committed to efforts in research and development, disease awareness as well as other activities in order to address the diverse needs of to those living with obesity – a chronic, progressive disease that has serious health consequences,” said Paul Hawthorne, Senior Vice President, Americas Neurology Business Unit, Neurology Business Group, Eisai Inc. “We are excited to offer patients a once-daily option for chronic weight management that may help them achieve and sustain their weight loss goals.”

Through the launch of BELVIQ XR, Eisai continues to make further contributions to address unmet medical needs in the clinical management of obesity and increase the benefits for patients and their families.

EISAI TO INITIATE PHASE III CLINICAL STUDY OF ANTICANCER AGENT LENVATINIB AS POTENTIAL FIRST-LINE THERAPY FOR ADVANCED RENAL CELL CARCINOMA

SIMULTANEOUS DEVELOPMENT OF TWO COMBINATION THERAPIES LENVATINIB/EVEROLIMUS AND LENVATINIB/PEMBROLIZUMAB

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today the initiation of a global Phase III Clinical Study (Study 307, CLEAR Study) of its in-house developed multiple receptor tyrosine kinase inhibitor lenvatinib mesylate (lenvatinib) in respective combination regimens with the anticancer agent everolimus and the anti-PD-1 antibody pembrolizumab as a potential first-line treatment for advanced renal cell carcinoma.

The CLEAR (Comparison of the efficacy and safety of Lenvatinib in combination with Everolimus or pembrolizumab versus sunitinib alone in first-line treatment of subjects with Advanced Renal cell carcinoma) study is a multicenter, randomized, open-label Phase III clinical study to compare the efficacy and safety of lenvatinib/everolimus and lenvatinib/pembrolizumab versus sunitinib alone in first-line treatment in patients with advanced renal cell carcinoma. The primary outcome measure will be progression-free survival.

Non-clinical research into the combination of lenvatinib and everolimus suggested synergistic enhancement of antiangiogenic activity and a stronger antitumor effect than either monotherapy in renal cell carcinoma models through the respective inhibition of signaling pathways which facilitate tumor angiogenesis, upstream (vascular endothelial growth factor receptor [VEGFR] and fibroblast growth factor receptor [FGFR]) with lenvatinib and downstream (mammalian target of rapamycin [mTOR]) with everolimus. Furthermore, non-clinical research into the combination of lenvatinib and anti-PD-1 antibody suggested that the combination has a mechanism of action in which lenvatinib enhances the antitumor activity of the anti-PD-1 antibody by reducing immunosuppressive cells.

The number of patients with renal cancer is estimated to be approximately 338,000 worldwide, including approximately 115,000 in Europe, 58,000 in the United States and 17,000 in Japan. Renal cell carcinoma comprises more than 90% of all malignancies of the kidney, and occurs when malignant cells are found 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 renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical need.

Currently lenvatinib has been approved in over 45 countries including the United States, Japan and in Europe as a treatment for refractory thyroid cancer. In May 2016, lenvatinib was approved in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy by the U.S. Food and Drug Administration in the United States. Furthermore, lenvatinib was approved in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor targeted therapy in Europe in August 2016.

Eisai regards oncology as a key therapeutic area and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai remains committed to providing further clinical evidence for lenvatinib aimed at 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.