Analysis Evaluates Efficacy of Eribulin in Metastatic HER2-low Breast Cancer Across Three Clinical Studies

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today results from a post hoc analysis of three randomized, pivotal, Phase 3 studies (EMBRACE trial/Study 305, Study 301 and Study304) evaluating the efficacy of eribulin mesylate (marketed as HALAVEN^?) versus other chemotherapies (Treatment of Physician’s Choice [TPC], capecitabine, and vinorelbine, respectively) in patients living with metastatic breast cancer (mBC) whose tumors have low or no HER2 expression. These data were presented as a poster (Presentation: #259P) at the European Society for Medical Oncology (ESMO) Annual Meeting (#ESMO22), held virtually and in-person in Paris, France from September 9-13, 2022.

The HER2-low breast cancer subtype is a newly defined subset consisting of tumors that would have previously been considered HER2-negative based on an immunohistochemistry (IHC) assay and an in situ hybridization (ISH) assay. HER2-low tumors express low amounts of the HER2 protein, but not enough to be considered HER2-positive. HER2-low is defined as an IHC of 1+ or 2 with a negative ISH. Of the approximate 288,000 new cases of female breast cancer expected to be diagnosed in the U.S. in 2022,¹ it is estimated that approximately 80-85% of patients would previously have been considered to have the HER2-negative subtype. Of those patients, about 60% would now be considered to have the HER2-low subtype.²

“In this post-hoc analysis, the outcomes seen in mBC patients whose tumors are considered HER2-low are consistent with the results of the three pivotal Phase 3 clinical trials,” said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President, Eisai Co., Ltd. “As the oncology community’s understanding of mBC continues to evolve, it’s important that we continue to evaluate the role of existing therapies in new contexts to contribute to the body of knowledge that is available to health care professionals.”

Data from the Post Hoc Analysis

The post hoc analysis included data from three trials — eribulin vs. TPC (NCT00388726, EMBRACE trial/Study 305), eribulin vs. capecitabine (NCT00337103, Study 301), and eribulin vs. vinorelbine (NCT02225470, Study 304) in patients with locally recurrent or mBC who had prior lines of chemotherapy treatments (≤2 for Study 301; 2-5 for Study 304 and EMBRACE Trial/Study 305) including an anthracycline and a taxane. A total of 1,589 eligible patients were enrolled in the EMBRACE trial/Study 305, Study 301 and Study 304, and baseline characteristics were generally balanced between treatment arms in all studies.

Median overall survival (OS), median progression free survival (PFS) and?objective response rate (ORR) were analyzed. PFS and ORR were measured per Response Evaluation Criteria in Solid Tumors Version (RECIST) (v1.0 for EMBRACE trial/Study 305 and Study 301; v1.1 for Study 304) by independent imaging review. ORR was measured in evaluable patients (EMBRACE trial/Study 305) and in the intent-to-treat population (Study 301 and Study 304).

In the post hoc analysis, OS, PFS, and ORR among patients with HER2-low or HER2-negative status were generally similar to those of the eribulin treatment arms overall in each of the EMBRACE trial/Study 305, Study 301 and Study 304.^3,4,5 Efficacy results for patients with HER2-low and HER2-negative status across all three studies are summarized in the table below:

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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its U.S. subsidiary Eisai Inc. has entered into a memorandum of understanding with C₂N Diagnostics (“C₂N”) that will seek to build awareness about how blood-based assays in the diagnosis for people living with cognitive impairment, including Alzheimer’s disease (AD), may help patients receive a timely diagnosis and appropriate treatment. Collaborating with C₂N, Eisai Inc. will work to build awareness and develop real-world evidence to support the use of blood-based assays in people living with cognitive impairment in clinical practice outside of clinical trial settings in the U.S. Blood-based assays could result in the development of new standards in clinical care that may enable timely and accurate diagnoses for people living with cognitive impairment.

The number of people with dementia is growing substantially; more than 55 million people worldwide are living with dementia, and this number is expected to increase to 78 million by 2030.¹ Accurate diagnosis remains a barrier to early and proper care management; research reviews estimate that between 40 and 60 percent of adults with probable dementia are undiagnosed.² Importantly, blood-based assays may be able to help identify which patients may benefit from therapy, and therefore may help streamline care and reduce healthcare spending. Early detection, diagnosis and treatment of dementia protects individuals against risks from delayed or missed diagnosis and allows individuals, their families and their caregivers to plan for the future as the condition progresses.²

The development and adoption of blood-based assays as simple diagnostic tools, in every day clinical practice is an important step in improving care for people in remote and underserved communities where access to the traditional diagnostic tools of positron emission tomography (PET) and lumbar punctures are not a viable option.

In collaboration with various partners, Eisai will engage in practical application of simple and less invasive diagnostic technologies and diagnostics for dementia, including blood tests, and will work to improve the medical environment in which people with dementia can receive appropriate treatment, thereby contributing to relieving anxieties of people living with dementia and their families around the world.

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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has been included in the FTSE4Good Index Series for the 21^st consecutive year since its initial inclusion in 2002. The FTSE4Good Index Series is a global index series for socially responsible investment.

The FTSE4Good Index Series was developed by FTSE Russell to promote investment in companies that meet global environmental, social and governance (ESG) standards. Eisai received particularly high scores in “Corporate Governance”, “Customer Responsibility”, “Labor Standards” and “Tax Transparency”, among others. As of the end of June 2022, 1,092 companies worldwide and 224 Japanese companies were included in the FTSE4Good Developed Index Series.

Currently, in addition to the MSCI ESG Leaders Indexes, another global ESG investment index, Eisai is also listed in the FTSE Blossom Japan Index, the FTSE Blossom Japan Sector Relative Index, the MSCI Japan ESG Select Leaders Index, the MSCI Japan Empowering Women Index (WIN) and the S&P/JPX Carbon Efficient Index, which are ESG investment indices for Japanese stocks adopted by the Government Pension Investment Fund (GPIF).

Eisai’s corporate concept is to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides to them, as well as address diverse healthcare needs worldwide. By strengthening its ESG initiatives and increasing non-financial value, Eisai is striving to sustainably enhance corporate value based on this concept.

For more information on our ESG initiatives, please visit https://www.eisai.com/sustainability/index.html.

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Second Publication on the Potential Value of Lecanemab in Patients with Early Alzheimer’s Disease Using Simulation Modeling

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) today announced publication of results from an early phase evaluation that aimed to estimate potential economic value of its investigational anti-amyloid-beta (Aβ) protofibril antibody lecanemab in people living with early Alzheimer’s disease (AD) using a validated disease simulation model, AD Archimedes Condition Event (AD ACE) model^1,2,3 from the healthcare payer and societal perspectives in the United States, in the peer-reviewed journal Neurology and Therapy. This is the second publication of lecanemab’s potential value. It follows the evaluation of the long-term health outcomes using simulation modeling of lecanemab published in Neurology and Therapy in April 2022.⁴ While the healthcare payer perspective focuses on direct care costs (e.g., outpatient and inpatient services, medications, intervention costs, nursing home and home healthcare services), the societal perspective further considers societal costs (e.g., productivity loss and informal care costs). As reported in the previous publication, it was suggested that compared to standard of care* (SoC), individuals treated with lecanemab in addition to SoC (lecanemab+SoC) may potentially experience slower disease progression to mild, moderate and severe AD from baseline by 2.51, 3.13 and 2.34 years on average, respectively. The preliminary results of this model-based simulation could possibly translate into additional quality-adjusted life years (QALY**) and reduction in the formal and informal care costs***. Additionally, the AD ACE model framework used in this study allowed assessment of the potential value of lecanemab in different scenarios and sensitivity analyses, including the impact of patient subsets, alternative treatment stopping rules**** and potential dosing regimens as well as major sources of uncertainty.

Eisai is committed to conducting and sharing these types of clinical and socioeconomic analyses to establish trust as we work to potentially bring lecanemab to people living with early AD who have confirmed presence of amyloid pathology in the brain. To that end, Eisai would like to provide a common foundation for stakeholders’ discourse regarding the potential clinical and socioeconomic value of lecanemab from the societal perspective, not to assign a price for lecanemab at this time.

This model-based simulation was conducted using the results of a Phase 2b clinical trial (Study 201) evaluating the efficacy and safety of lecanemab for early AD with confirmed amyloid pathology as well as published literature. It also estimated the potential economic value of lecanemab+SoC over a broad range of willingness-to-pay thresholds from $50,000 to $200,000 per QALY gained as recommended by the Institute for Clinical and Economic Review (ICER)*****. Lecanemab+SoC was predicted to result in a gain of 0.61 QALYs and a decrease in total non-treatment costs of $8,707 per person from the healthcare payer perspective (Societal perspective: 0.64 QALYs gain and $11,214 decrease) compared to the SoC for patients with early AD who have confirmed presence of amyloid pathology. The potential annual value-based price (VBP) of lecanemab was estimated at $9,249 to $35,605 (Societal perspective: $10,400 to $38,053) based on this early economic assessment.

ICER’s value framework⁵ indicates that value cannot be wholly derived from measures of clinical and cost-effectiveness, so contextual considerations and an examination of other benefits and disadvantages are also added into the framework when assessing long-term value. This may lead to using the societal perspective and higher end of the broad range of willingness-to-pay threshold in estimating the justifiable price of lecanemab, given the large societal burden of AD relative to direct healthcare costs.

Many people living with AD received informal care from their family and friends totaling more than 16 billion hours of unpaid care valued at $271.6 billion in the U.S. in 2021.⁶ These predicted and simulated findings suggest that early treatment with lecanemab may reduce these costs and economic burdens, and provide insights for healthcare decision-makers regarding the potential clinical and socioeconomic value of lecanemab. The Phase 3 lecanemab Clarity AD data will soon be available to inform the model inputs and refine the findings. In the event that lecanemab receives the U.S. Food and Drug Administration’s (FDA) approval, Eisai may determine a VBP using this framework along with other considerations, such as affordability, health system sustainability, etc.

“Eisai’s goal is to create therapies, such as our investigational anti-amyloid beta protofibril antibody lecanemab, that may help impact the anxieties of people living with Alzheimer’s disease and their families. For Alzheimer’s disease, it is important to evaluate the holistic value of therapies taking into account not only medical costs but also the immense societal costs,” said Ivan Cheung, Senior Vice President, President Neurology Business Group and Global Alzheimer’s Disease Officer, Eisai Co., Ltd., Chairman and CEO, Eisai Inc. “As part of Eisai’s commitment to our human health care mission, trust and transparency, we will continue to publish data and information about lecanemab and look forward to sharing the results of the lecanemab confirmatory Phase 3 Clarity AD clinical trial this fall.”

Eisai completed lecanemab’s rolling submission of a Biologics License Application (BLA) for the treatment of early AD to the FDA under the accelerated approval pathway in May 2022. The Clarity AD Phase 3 clinical study for lecanemab in early AD is ongoing and completed enrollment in March 2021 with 1,795 patients. The readout of the primary endpoint data of Clarity AD will occur in the fall of 2022. The FDA has agreed that the results of Clarity AD, when completed, can serve as the confirmatory study to verify the clinical benefit of lecanemab. Dependent upon the results of the Clarity AD clinical trial, Eisai may submit for full approval of lecanemab to the FDA during Eisai’s fiscal year 2022, which ends in March2023. In Japan, in March 2022, Eisai initiated submission of application data to the Pharmaceuticals and Medical Devices Agency (PMDA) under the prior assessment consultation system with the goal of obtaining early approval for lecanemab, and aims to file for the manufacturing and marketing approval based on the results of Clarity AD during Eisai’s fiscal year 2022. Also, in Europe, based on the results of the Clarity AD study, Eisai plans to submit a new drug application in fiscal year 2022.

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.

* ?Standard of Care (SoC) for AD currently consists of lifestyle modifications and pharmacologic treatment of symptoms.

** The quality-adjusted life year (QALY) is a measure of the value of health outcomes. Since health is a function of length of life (i.e., quantity) and quality of life (QOL), the QALY was developed as an attempt to combine the value of these attributes into a single index number. One QALY equates to one year in perfect health. QALY scores range from 1 (full health) to 0 (dead). For example, a new intervention may increase length of life by 3 years and improve quality of life by 70% (QALY score of 2.1) compared to an existing intervention that may increase length of life by 3 years and only improve QOL by 50% (QALY score of 1.5), the incremental QALY for this new intervention will be 0.6 QALYs.

*** Formal and informal care costs do not include lecanemab drug cost.

**** Alternative treatment stopping rules were explored in scenario analyses where treatment with lecanemab was stopped after a fixed duration of 1.5, 3 and 5 years.

***** ICER is a non-profit research organization in the U.S. that evaluates the evidence on the clinical and economic value of prescription drugs, medical tests, devices and health system delivery innovations.

¹ Kansal AR, Tafazzoli A, Ishak KJ, Krotneva S. Alzheimer’s disease Archimedes condition-event simulator: Development and validation. Alzheimers Dement (NY). 2018;4:76-88. Published 2018 Feb 16. doi:10.1016/j.trci.2018.01.001.

² Tafazzoli and Kansal. Disease simulation in drug development, External validation confirms benefit in decision making. The Evidence Forum. 2018.

https://www.evidera.com/wp-content/uploads/2018/10/07-Disease-Simulation-in-Drug-Development_Fall2018.pdf

³ Tafazzoli A, Weng J, Sutton K, et al. Validating simulated cognition trajectories based on ADNI against 436 trajectories from the National Alzheimer’s Coordinating Center (NACC) dataset. 11th edition of Clinical Trials on 437 Alzheimer’s Disease (CTAD); Barcelona, Spain: 2018.

⁴ Tahami Monfared AA, Tafazzoli A, Ye W, Chavan A, Zhang Q. Long-Term Health Outcomes of Lecanemab in Patients with Early Alzheimer’s Disease Using Simulation Modeling. Neurol Ther 11, 863–880 (2022). https://link.springer.com/article/10.1007/s40120-022-00350-y.

⁵ ICER Value Framework 2020-2023. 2022. ICER_2020_2023_VAF_02032022.pdf

⁶ Alzheimer’s Association. 2022 Alzheimer’s Disease Facts and Figures 2022 Available from: alzheimers-facts-and-figures.pdf.

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Libby Holman

Libby_Holman@Eisai.com

201-753-1945

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it was selected as the winner of the Tokyo Governor Prize for Corporate Governance of the Year^? 2021, which is an award program organized by the Japan Association of Corporate Directors (JACD; Chairman: Yoshihiko Miyauchi). The award ceremony was held on January 31, 2022.

The awards have been established to recognize the companies which have achieved and maintained the medium to long term profitability by implementing good corporate governance, since 2015. Among the eligible companies for selection of the Corporate Governance of the Year 2021, the Tokyo Governor Prize goes to a company which has excellent corporate governance and also practices ESG activities such as environmental activities, women empowerment, initiatives for diversity and work style reforms.

Commenting on the reason for selecting Eisai, Mr. Eiichiro Kodama, Director General for Global Financial City Strategy, Office of the Governor for Policy Planning, Tokyo Metropolitan Government stated, “Eisai is a pioneer in incorporating its corporate philosophy into the Articles of Incorporation and practicing “Purpose Management.” With regard to corporate governance, Eisai makes the most of its status as a company with a nomination committee, etc., system to clearly separate management oversight and business execution, and places great importance to dialogue with its stakeholders including patients. In terms of ESG, Eisai is a signatory to the United Nations Global Compact and actively participates in climate change-related initiatives such as “RE100” and the Japan Climate Initiative. In addition, Eisai is taking on the challenge of quantifying values that do not appear on the balance sheet, such as investments in human capital, with attempting to select KPIs related ESG including the ratio of women in management positions, analyze its relationship with PBR (Price Book-value Ratio), and utilize the verification results for engagement with investors. Eisai is actively working to tell the story of the cause-and-effect relationship between the ESG initiatives and the enhancement of corporate value, thus taking on the extremely important challenge to visualize invisible value, embody the value of ESG, and disseminate them.”

Eisai defines its corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides” in the Articles of Incorporation, and shares it with its stakeholders. Eisai calls this philosophy the human health care?(hhc) philosophy, in one word, and believes that practicing philosophical management based on the hhc philosophy will contribute to achieving Sustainable Development Goals (SDGs) and further enhance its corporate value.

Eisai is committed to further strengthening its corporate governance in order to realize the?hhc?philosophy.