Eisai Furthers Oncology Research Across Multiple Cancers at ASCO GI and ASCO GU 2024

by codm | Jan 16, 2024 | Newsletter

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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today the presentation of oncology research at two upcoming medical meetings taking place in-person in San Francisco, California and virtually. First, the company will share findings in hepatocellular carcinoma (HCC) and cholangiocarcinoma during the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium (#GI24), which is taking place from January 18-20. Eisai will also present research results in renal cell carcinoma (RCC) during the 2024 ASCO Genitourinary Cancers Symposium (#GU24), which is taking place from January 25-27.

Key Data from Eisai’s Pipeline and Portfolio to be Presented at ASCO GI 2024
Notable findings from Eisai’s pipeline include results from a single-arm Phase 2 trial evaluating tasurgratinib (formerly E7090) as a treatment for patients with fibroblast growth factor receptor 2 (FGFR2) gene fusion positive cholangiocarcinoma (NCT04238715; Abstract: #471). Tasurgratinib, for which a marketing authorization application was submitted in Japan in December 2023, is an orally available selective tyrosine kinase inhibitor of FGFR1-3. An analysis of tumor biomarkers in patients with advanced HCC from a Phase 1b study of E7386^*1, a CREB-binding protein (CBP) / β-catenin interaction inhibitor, in combination with lenvatinib, will also be presented (NCT04008797; Abstract: #535).

Additional data from the LEAP (LEnvatinib And Pembrolizumab) clinical program include longer term efficacy and safety results from the Phase 3 LEAP-002 trial, which evaluated lenvatinib (LENVIMA^®), the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, plus pembrolizumab (KEYTRUDA^®*2), the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA, versus lenvatinib monotherapy as a first-line treatment for patients with unresectable HCC (NCT03713593; Abstract: #482).

The list of notable ASCO GI 2024 presentations is included below. These abstracts will be made available via the ASCO website on Tuesday, January 16, 2024, at 2:00 PM PST.

Key Data from Eisai’s Pipeline and Portfolio to be Presented at ASCO GU 2024
Subgroup analyses from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, which evaluated lenvatinib plus pembrolizumab versus sunitinib for the first-line treatment of patients with advanced renal cell carcinoma (aRCC), will be featured in a rapid oral abstract session (NCT02811861; Abstract: #364) and a network meta-analysis to assess the efficacy of lenvatinib plus pembrolizumab compared with other first-line treatment options for patients with aRCC will also be presented in a poster session (Abstract: #482). Extended follow-up results from the Phase 2 KEYNOTE-B61 trial evaluating the combination as a first-line treatment for patients with non-clear cell RCC will be shared in a poster presentation (NCT04704219; Abstract: #2) by Merck & Co., Inc., Rahway, NJ, USA. Finally, a poster featuring real-world evidence on the use of lenvatinib plus everolimus in previously treated patients with aRCC (Abstract: #437) will also be presented.

The list of notable ASCO GU 2024 presentations is included below. These abstracts will be made available via the ASCO website on Monday, January 22, 2024, at 2:00 PM PST.

In March 2018, Eisai and Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA, pembrolizumab. Eisai and Merck & Co., Inc., Rahway, NJ, USA are studying the lenvatinib plus pembrolizumab combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor types across multiple clinical trials.

This release discusses investigational compounds and investigational uses for Food and Drug Administration (FDA)-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

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

[Notes to editors]
1. Eisai’s Focus on Cancer
Eisai acknowledges “Oncology” as one of its key strategic areas, and will continue to focus on the discovery and development of anti-cancer drugs within drug discovery domains including “microenvironment”, “proteostasis disruption”, “cell lineage and cell differentiation”, and “inflammation, hypoxia, oxidative stress and cell senescence” under the Deep Human Biology Learning (DHBL) drug discovery and development organization. Eisai aspires to discover innovative new drugs with new targets and mechanisms of action from these domains, with the aim of contributing to the cure of cancers.

*1 E7386 is created through collaboration research between Eisai and PRISM BioLab Co., Ltd. (Headquarters: Kanagawa)
*2 KEYTRUDA^® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, N.J., U.S.A.

THE SCIENTIFIC ADVISORY GROUP (SAG) TO CONVENE TO DISCUSS THE MARKETING AUTHORIZATION APPLICATION FOR LECANEMAB IN THE EU

by codm | Jan 11, 2024 | Newsletter

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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the Scientific Advisory Group (SAG) will convene to discuss the marketing authorization application (MAA) of lecanemab (generic name, brand name: LEQEMBI^®), which is currently under review by the European Medicines Agency (EMA). The meeting of the SAG is expected to take place during FY2023, which ends on March 31, 2024.

The SAG is convened at the request of the Committee for Medicinal Products for Human Use (CHMP) of the EMA to provide independent advice on scientific or technical matters relating to products under evaluation by the CHMP, or on other scientific issues relevant to the work of the CHMP.

Eisai expects the European Commission’s decision for the MAA of lecanemab in the first quarter of FY2024 ending June 30, 2024, if the opinion from the CHMP is received by March 31, 2024, following discussion by the SAG.

Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen Inc. (U.S.) co-commercializing and co-promoting the product and Eisai having final decision-making authority.

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

[Notes to editors]
1.  About Lecanemab (generic name, brand name: LEQEMBI^®),
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted traditional approval by the U.S. Food and Drug Administration (FDA) on July 6, 2023. LEQEMBI is an amyloid beta-directed antibody indicated as a disease-modifying treatment for Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. In Japan, Eisai received approval from the Ministry of Health, Labour and Welfare (MHLW) on September 25, 2023, to manufacture and market LEQEMBI as a treatment for slowing progression of MCI and mild dementia due to AD. Furthermore, in China, LEQEMBI was approved by the National Medical Products Administration (NMPA) as a treatment of mild cognitive impairment (MCI) due to AD and mild AD dementia on January 5, 2024.
Please see full U.S. Prescribing Information for LEQEMBI, including Boxed WARNING.

Eisai has also submitted applications for approval of lecanemab in Canada, Great Britain, Australia, Switzerland, South Korea and Israel in addition to EU. In Israel the application has been designated for priority review, and in Great Britain lecanemab has been designated for the Innovative Licensing and Access Pathway (ILAP), which aims to reduce the time to market for innovative medicines.

Eisai has completed a lecanemab subcutaneous bioavailability study, and subcutaneous dosing is still being evaluated in the Clarity AD (Study 301) open-label extension (OLE). A maintenance dosing regimen has been evaluated as part of Study 201.

Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.

Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.

2.  About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.

3.  About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.

“LEQEMBI®” (Lecanemab) Approved for the Treatment of Alzheimer’s Disease in China

by codm | Jan 9, 2024 | Newsletter

China is the Third Country to Approve LEQEMBI Following the United States and Japan

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TOKYO and CAMBRIDGE, Mass., January 9, 2024 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, “Biogen”) announced today that humanized anti- soluble aggregated amyloid-beta (Aβ) monoclonal antibody “LEQEMBI^®” (brand name in China: “乐意保^®”, generic name: lecanemab-irmb) has been approved in China as a treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD dementia. Preparations for launch within the second quarter of Eisai’s FY 2024 (July 1 – September 30, 2024) are underway.

LEQEMBI selectively binds to soluble Aβ aggregates (protofibrils*), as well as insoluble Aβ aggregates (fibrils) which are a major component of Aβ plaques, thereby reducing both Aβ protofibrils and Aβ plaques in the brain. LEQEMBI is the first and only approved treatment shown to reduce the rate of disease progression and to slow cognitive and functional decline through this mechanism. China is the third country to grant marketing approval, following the traditional approval in the U.S. in July 2023 and Japanese approval in September 2023.

LEQEMBI’s approval in China is based on the large global Phase III Clarity AD study. In the Clarity AD study, LEQEMBI met its primary endpoint and all key secondary endpoints with statistically significant results. In November 2022, the results of the Clarity AD study were presented at the 2022 Clinical Trials on Alzheimer’s Disease (CTAD) conference, and simultaneously published in the New England Journal of Medicine, a peer-reviewed medical journal.

Eisai estimates that there will be 17 million patients with MCI or mild dementia due to AD in China in 2024, which is expected to increase with the aging of the population. Eisai will distribute the product in China and will conduct information provision activities through specialized Medical Representatives. Moving forward, Eisai will focus on AD awareness via omnichannel systems and collaborate with specialists to improve the diagnostic environment, including blood-based biomarkers. In addition, by utilizing online health platform for the elderly “Yin Fa Tong”**, which is already being accessed by a certain number of users and helping provide treatments, Eisai is providing a one-stop service that promotes early consultation by referring patients to medical specialists and follow-up after treatment. In addition, Eisai will work to improve access environments including the development of insurance programs for AD in collaboration with insurance companies. Through these efforts, Eisai will accelerate the construction of a simple patient journey in China.

^*   Protofibrils are large Aβ aggregated soluble species of 75-5000 Kd.^1,2,3.
^** An online business (Chinese name:銀髪通) of Jingyi Weixiang (Shanghai) Health Industry Development Limited Company, a joint venture company with JD Health.

MEDIA CONTACTS

INVESTOR CONTACTS

1. “乐意保^®” (LEQEMBI^®) Product Outline
Chinese Trade name: “乐意保” (LEQEMBI)
Chinese generic name: 仑卡奈单抗注射液 (lecanemab injection)
Indication for use: Treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD dementia
Dosage and administration: The usual dose of lecanemab (recombinant) is 10mg/kg infused intravenously over approximately 1 hour, once every 2 weeks.
Active ingredients and strength: 200mg (2mL)/1 vial and 500mg (5mL)/1 vial

2. About LEQEMBI
LEQEMBI (lecanemab) is the result of a strategic research alliance between Eisai and BioArctic. LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). LEQEMBI is an amyloid beta-directed antibody indicated as a disease-modifying treatment for Alzheimer’s disease (AD) in the U.S. The U.S. Food and Drug Administration (FDA) granted traditional approval on July 6, 2023. In the U.S., treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.
Please see full U.S. Prescribing Information for LEQEMBI, including Boxed WARNING.

In Japan, Eisai received approval from the Ministry of Health, Labour and Welfare (MHLW) on September 25, 2023, to manufacture and market lecanemab as a treatment for slowing progression of mild cognitive impairment (MCI) and mild dementia due to AD.

LEQEMBI’s approval was based on Phase 3 data from Eisai’s large, global Clarity AD clinical trial, in which LEQEMBI met its primary endpoint and all key secondary endpoints with statistically significant results and confirmed the clinical benefit of LEQEMBI. The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with LEQEMBI reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo. In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo. The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the LEQEMBI group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall. Full results of the Clarity AD study were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) 2022 conference and simultaneously published in the peer-reviewed medical journal The New England Journal of Medicine(New Window) on November 29, 2022.

Eisai has also submitted applications for approval of lecanemab in 11 countries and regions, including EU, Canada and Great Britain.

Eisai has completed a lecanemab subcutaneous bioavailability study, and subcutaneous dosing of lecanemab is currently being evaluated in the Clarity AD (Study 301) open-label extension (OLE). A maintenance dosing regimen has been evaluated as part of Study 201.

Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.

3. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.

4. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.

5. About Eisai Co., Ltd.
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.” Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.

In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.

For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on X, LinkedIn and Facebook.

6. About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, two co-developed treatments to address a defining pathology of Alzheimer’s disease, the first treatment to target a genetic form of ALS, the first oral treatment approved for postpartum depression, and the first approved treatment for Friedreich’s ataxia. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.

The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media –Facebook, LinkedIn, X, YouTube.

Biogen Safe Harbor
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential clinical effects of LEQEMBI; the potential benefits, safety and efficacy of LEQEMBI; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer’s disease; the anticipated benefits and potential of Biogen’s collaboration arrangements with Eisai; the potential of Biogen’s commercial business and pipeline programs, including  LEQEMBI; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation unexpected concerns that may arise from additional data, analysis or results obtained during clinical studies, including the Clarity AD clinical trial and AHEAD 3-45 study; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; regulatory submissions may take longer or be more difficult to complete than expected; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen’s drug candidates, including LEQEMBI; actual timing and content of submissions to and decisions made by the regulatory authorities regarding LEQEMBI; uncertainty of success in the development and potential commercialization of LEQEMBI; failure to protect and enforce Biogen’s data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on Biogen’s business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen’s expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in Biogen’s most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements a speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements.

References

1. https://www.alzforum.org/news/conference-coverage/lecanemab-sweeps-toxic-av-protofibrils-catches-eyes-trialists
2. Sehlin D, Englund H, Simu B, Karlsson M, Ingelsson M, Nikolajeff F, Lannfelt L, Pettersson FE. Large aggregates are the major soluble Aβ species in AD brain fractionated with density gradient ultracentrifugation. PLoS One. 2012;7(2):e32014. https://doi.org/10.1371/journal.pone.0032014 Epub 2012 Feb 15. PMID: 22355408; PMCID: PMC3280222.
3. Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics. 2023;20:195-206. https://doi.org/10.1007/s13311-022-01308-6

EISAI SUPPORTS RELIEF EFFORTS FOR THE NOTO PENINSULA EARTHQUAKE OF 2024 IN JAPAN

by codm | Jan 5, 2024 | Newsletter

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We extend our deepest sympathies to those affected by the Noto Peninsula Earthquake in Japan.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has decided to offer a donation of 35 million yen to medical associations and pharmaceutical associations in areas where damage is particularly extensive to support medical activities in the afflicted regions. In addition, Eisai will provide aid supplies hygienic materials such as anti-microbial spray and sterilized wipes, as well as vitamin drinks to medical institution, nursing care facilities and others in the affected regions.

Eisai sincerely prays for the rapid recovery of the afflicted regions.

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

DEVELOPMENT OF PREDICTION MODEL FOR BRAIN AMYLOID-BETA ACCUMULATION USING WRISTBAND SENSOR

by codm | Dec 26, 2023 | Newsletter

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Oita University and Eisai Co., Ltd. (Eisai) hereby announce the development of the world’s first machine learning model to predict amyloid beta*¹ (Aβ) accumulation in the brain using a wristband sensor. This model is expected to enable screening for brain Aβ accumulation, which is an important pathological factor of Alzheimer’s disease*² (AD), simply by collecting biological and lifestyle data from daily life.

The details of this model were published in the online edition of the peer-reviewed medical journal Alzheimer’s Research & Therapy on December 12, 2023.

In AD, which is said to account for over 60% of the causes of dementia, Aβ begins to accumulate in the brain about 20 years before the onset of the disease. This has prompted the development of new therapeutic drugs targeting Aβ, leading to the approval of an humanized anti-soluble aggregated Aβ monoclonal antibody in Japan. The key to maximizing treatment effects of the medicine is detecting Aβ accumulation in the brain of patients with mild cognitive impairment before the onset of symptoms. Currently, although brain Aβ accumulation can be detected by positron emission tomography*³ (amyloid PET) and cerebrospinal fluid testing*⁴ (CSF testing), the number of medical institutes able to perform those tests is limited, and the high cost and invasiveness of these tests are considered issues. Therefore, development of an inexpensive and easy-to-use screening method has been sought after to identify those who need amyloid PET or CSF testing.

Although lifestyle factors, including lack of exercise, social isolation, and sleep disorders, as well as diseases, including hypertension, diabetes, and cardiovascular disease are known risk factors for AD, thus far, studies applying machine learning models to predict brain Aβ accumulation have used only cognitive function tests, blood tests, and brain imaging tests. In contrast, this is the first machine learning study to focus on “biological data” and “lifestyle data.”

This study integrated “biological data” collected by wristband sensors, such as physical activity, sleep, and heart rate, “lifestyle data” obtained from medical consultations, such as number of household members, employment status, frequency of going outdoors, means of transportation, number of days participating in community activity, and “subjects’ background”, such as age, education history, history of alcohol intake, and medical history (hypertension, stroke, diabetes, heart disease, thyroid disease) to create a machine learning model to predict individuals who are likely to test positive by brain amyloid PET, and evaluated the model’s performance. The result of this study showed that the Area Under the Curve (AUC), an evaluatioin index of the prediction model consisting of “biological data”, “lifestyle data” and “subjects’ background”, was 0.79, leading to the decision that the model has sufficient capability for screening. This machine learning model is able to predict brain Aβ accumulation using readily available non-invasive variables. As a result, this model appears widely applicable as a pre-screening for people living in areas with little access to amyloid PET and CSF testing, and to reduce financial and physical burden to patients, as well as the costs of clinical studies.

【Glossary of Terms】
*¹ Amyloid beta: A protein viewed as a cause of Alzheimer’s disease, which accumulates in the brain for about 20 years prior to the onset of the disease and forms senile plaques
*² Alzheimer’s disease: the most common cause of dementia, and its pathological characteristics include senile plaques, neurofibrillary tangles, and neuronal cell death
*³ Amyloid PET: a brain imaging test visualizing Aβ accumulation in the brain
*⁴ Cerebrospinal fluid testing: A test analyzing cerebrospinal fluid for Aβ42, phosphorylated tau, and total tau as biomarkers of Alzheimer’s disease

Background and Outline of Research
As Japan has become a super-aging society with the rise in the number of dementia patients over the age of 65, the development of new therapeutic agents for AD, the most common cause of dementia, is an urgent issue. Lifestyle habits such as lack of exercise, social isolation, and sleep disorders, as well as diseases such as hypertension, diabetes, and cardiovascular disease, are known risk factors for AD. The development of drugs targeting Aβ has seen progress in recent years, and this year, an anti-Aβ protofibril antibody was approved in Japan. To maximize the effects of this medicine, it is essential to identify individuals with pre-symptomatic mild cognitive impairment (MCI) who are likely to have elevated brain amyloid accumulation. To date, although reports on machine learning models for predicting brain Aβ accumulation by cognitive function tests, blood tests, and brain imaging tests have been available, no research has focused on biological data or lifestyle data. This research is the world’s first attempt to create a machine learning model to predict amyloid positivity in subjects by utilizing “biological data” collected with a wristband sensor, including daily activity, sleep, speech, and heart rate, and “lifestyle data” collected through medical consultation.

Results and Significance of Research, Future Development
This research utilized data from a prospective cohort study on the elderly without dementia aged 65 and older living in Usuki City, Oita Prefecture, conducted between August 2015 and September 2019. 122 individuals (54 men, 68 women, median age 75.50 years) with mild cognitive impairment or subjective memory impairment wore a wristband sensor for approximately 7 days every 3 months. The study also collected lifestyle data through medical consultation, and subjects underwent regular amyloid PET (once a year) examinations over the course of 3 years. The research evaluated a predictive model created with three machine learning technologies, support vector machine, Elastic Net, and logistic regression, to integrate “Biological data” collected by wristband sensors, such as physical activity, sleep, and heartbeat, and “lifestyle data” obtained from medical consultations, such as living with household members, employment status, frequency of going outdoors, means of transportation, number of days participating in community activity, as well as the “subjects’ background”, such as age, education history, history of alcohol use, and medical history (hypertension, stroke, diabetes, heart disease, thyroid disease). For instance, while  the AUC of a predictive model created with only “biological data” collected by the wristband sensors using Elastic Net was 0.70, the AUC of a predictive model created with additional “lifestyle data” and patient background was 0.79, exhibiting improved performance. This research is the world’s first attempt to create a machine learning model to predict brain Aβ accumulation by utilizing “biological data” collected with a wristband sensor, including daily activity, sleep, speech, and heart rate, and “lifestyle data” collected through medical consultation, as well as “subjects’ background”

Furthermore, using state-of-the-art algorithms the to identify multiple factors which contribute to predicting Aβ accumulation, 22 common factors were identified that were common across the three learning machine technologies. Specifically identified were physical activity, sleep, heart rate, amount of conversation, age, length of education, living with or without children, means of transportation, presence of accompanying person for hospital visits, communication frequencies, and number of outings.

Academic Paper:
Title: Predicting positron emission tomography brain amyloid positivity using interpretable machine learning models with wearable sensor data and lifestyle factors
Authors: Noriyuki Kimura (Department of Neurology, Faculty of Medicine, Oita University) 1,2, Tomoki Aota (Eisai Co., Ltd.) 1, Yasuhiro Aso(Oita Prefectural Hospital), Kenichi Yabuuchi (Department of Neurology, Faculty of Medicine, Oita University), Kotaro Sasaki (Eisai Co., Ltd.), Teruaki Masuda (Department of Neurology, Faculty of Medicine, Oita University), Atsuko Eguchi(Department of Neurology, Faculty of Medicine, Oita University), Yoshitaka Maeda (Eisai Co., Ltd.), Ken Aoshima (Eisai Co., Ltd./University of Tsukuba) 2, Etsuro Matsubara (Department of Neurology, Faculty of Medicine, Oita University)
1. These authors contributed equally to the manuscript.
2. Corresponding author.
Publisher:    Alzheimer’s Research & Therapy

Please direct any interview requests or inquiries to the contact information provided below
For further information or any inquiries regarding this study
Noriyuki Kimura, Associate Professor, Department of Neurology, Faculty of Medicine, Oita University
TEL: +81-(0)97-586-5814, FAX: +81-(0)97-586-6502
Email：naika3@oita-u.ac.jp

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