EISAI DEMENTIA PLATFORM EASIIT COMMENCES

 

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and DeNA Co., Ltd.’s subsidiary DeSC Healthcare Co., Ltd. (Headquarters: Tokyo, CEO: Sho Segawa, CMO: Kuniaki Miyake, “DeNA”) announced that they have begun provision of the brain performance application “Easiit” (non-medical device, referred to below as “Easiit App”), for preparation against dementia, on July 28, 2020. This provision is based on a business alliance agreement aiming for support and creation of new solutions in the dementia area as well as co-development of the Easiit App as a base element of the digital platform for dementia that Eisai is currently constructing. With the beginning of provision of the Easiit App, the Eisai Dementia Platform Easiit has commenced.

Eisai possesses over 35 years of experience in medicine creation and business activity in the dementia field, and DeNA has demonstrated performance in providing healthcare services and altering consumer behavior while applying know-how from its gaming and sports industry experiences with the theme of “Staying healthy with fun”. Both companies aim to contribute towards better health practices by all people through such approaches as visualizing brain and body health data, supporting brain performance maintenance, and providing useful lifestyle information. Both companies will continue their efforts in partnership for creating the digital platform, including the expansion of functions of the Easiit App.

 

Background on the co-development and provision of the Easiit App

In its medium-term business plan, EWAY2025, Eisai is aiming to become a “Medico Societal Innovator”, a company that changes society through creating medicines and providing various innovative solutions that change society. Particularly in the dementia field, Eisai is collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, fitness clubs, automobile makers, retailers, and care facilities to realize construction of a “Dementia Ecosystem” for delivering new benefits. The base of this ecosystem will be the Dementia Platform Easiit. Through this platform, Eisai aims to collect information from participants, combine this information with Eisai’s independent data set comprising elements such as know-how, experience, and clinical data, and perform analysis in compliance with relevant regulations in order to deliver new benefits to participants in the form of various healthcare predictions and advice.

DeNA’s healthcare business aims for the extension of “healthy life expectancy” by realizing the conversion of “sick care” through treatment after becoming sick to “healthcare” through preventing sickness from occurring. DeNA provides various internet based healthcare services that apply its unique know-how for making enjoyable user experiences and extending use as cultivated through its activities in the gaming and sports fields.

In recent years, various research has demonstrated the possibility that decline in brain health may be mitigated through readjustments to lifestyle such as regular exercise, a well-balanced diet, and social interaction. On the other hand, according to a survey conducted by Eisai, the number of people who understand the correct preventive measures or perform cognitive function checks regularly are few, which indicates disparities (“chasms”).

The Easitt App, which aims to contribute to the promotion of healthy habits by making brain and body health visible, is core to Eisai’s digital platform business directed at eliminating these chasms. Both companies combined their respective strengths to co-develop this app, and have now begun provision of the first version.

 

The brain performance app “Easiit App”

In the Easiit App, a menu of individualized recommendations based on users’ footsteps, diet, sleep, and weight records (lifelog) is updated on a weekly basis and displayed. Individualized scoring is conducted based on actions and habits which are good for brain performance. The Easiit App confirms score changes and breakdown, and encourages formation of good habits for brain performance moving forward. For diet record in particular, easy diet management is made possible as the Easiit App evaluates users’ meals via photo upload for calorie intake and eleven essential nutrients, and displays this information in relation to an age-based standard for calorie and nutrient intake. Additionally, with every use of the app one can collect Easiit miles, which can be exchanged for prizes such as gift cards. Through connection to wearables and subsequent functions such as sleep time tracking, the Easiit App can encourage the creation of good habits for brain performance.

All of the functions within the Easiit App are designed, developed, and operated on a framework for protection of individual information.

Planned functions moving forward

In the end of September of this year, Eisai plans to equip the Easiit App with a linkage to the brain performance self-check tool “NouKNOW” (non-medical device), which Eisai is currently selling to legal entities. In the future, the addition of a new function is planned for use in families in which members are living separately from each other.

Additionally, Eisai is investigating future equipment of the Easiit App with a function allowing for connection to medical data (as a non-medical device) on top of daily lifestyle data.

 

Commentary from persons in charge of operations in both companies

Eisai Vice President, President of Dementia Total Inclusive Ecosystem Business Unit and Chief Digital Officer Keisuke Naito said, “I believe that recording the health state of one’s brain and body alike and making those records visible is critical to the realization of one’s well-being in one’s own way. This app, which we have co-developed with DeNA, enables one to easily record one’s footsteps, sleep time, diet, nutrient deficiencies, and other elements. Through the expansion and wide adoption of the Easiit App, we will work steadfastly in this first step towards the realization of a society in which anyone may measure their own brain performance easily, make lifestyle improvements for the future, and receive early stage medical examination.”

DeNA Vice President, Head of Healthcare Business Division and President of DeSC Healthcare Co., Ltd. Sho Segawa said, “I encountered Eisai at a time when I was watching my parents care for my grandfather, who had developed dementia, and thinking to myself, ‘Is there not something I can do as a player of the healthcare industry?’. With the combination of Eisai’s experience in the dementia field and DeNA’s services, we will concentrate our expertise for encouraging and sustaining enjoyable healthy lifestyles in the Easiit App, making an effort to accelerate the creation of solutions for dementia.”

 

[Notes to editors]

1.?About brain performance (brain health) and issues surrounding it

In recent years, various research has demonstrated the possibility that decline in brain performance (brain health) may be mitigated through major readjustments to lifestyle such as regular exercise, a well-balanced diet, and social interaction. On the other hand, according to survey* conducted by Eisai on men and women in Japan between forty and seventy-nine years of age, it was revealed that 55.7% of participants understood the meaning and contents behind early assessment and prevention, 19.7% of participants were taking correct preventive actions in diet, exercise, sleep, etc. on a regular basis, and no more than 2.1% of participants were habitually performing self-assessments of cognitive function. These statistics represent disparities (“chasms”) which must be overcome in order to promote disease understanding and the incorporation of cognitive function checks into daily lifestyle.

*Independent online survey conducted in December 2019 by Eisai in Japan on participants in their 40’s, 50’s, 60’s, and above 70, with 200 male and 200 female participants per age bracket (total: 1,600).

 

2.?Summary of Easiit App details

Availability: iOS version available July 28, 2020 (Tuesday), Android version planned availability for end of August 2020.

Cost: Free of charge; the high function edition with various additional contents and continuous individual data visualization is to be launched for a charge in the winter of 2020.

 

Supervising editor: Dr.?Atsushi Iwata, Director, Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Easiit website:?https://www.easiit.com/app

 

<Functions, properties>

• Presents weekly menu customized for the user, including suggestions for exercise, diet, sleep, etc.
• Presents footstep count, diet record, sleep time, and body weight in graph form for user confirmation
• Evaluates users’ meal photos for amount of calories and eleven essential nutrients and displays this information in relation to an age-based standard for intake
• Awards Easiit miles with every use, which can be collected and exchanged for gift cards, etc.
• Connects with the Fitbit wearable device to automate footstep count, sleep time, and body weight measurement
• Conducts individual scoring [Easiit Score] based on records of actions and habits which are good for brain performance in correspondence with the menu. The Easiit Score provides a positive motivation for the user to practice a lifestyle that is good for brain performance.

3. About the Dementia Ecosystem business

Leveraging experience gained from the development and marketing of Aricept^?, a treatment for Alzheimer’s disease and dementia with Lewy bodies, Eisai aims to establish the “Dementia Platform Easiit” for analyzing participants’ health and lifestyle information and subsequently providing advice on brain health. In the future, Eisai is planning to evolve this platform to a digital platform that spans areas of daily life and medicine.

With the digital platform as a base, Eisai aims to construct a “Dementia Ecosystem” for delivering new benefits by collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, finance, fitness clubs, automobile makers, retailers, and care facilities.

 

4. About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. Eisai’s corporate philosophy is based on the?human health care?(hhc) concept, which is to give first thought to patients and their families, and to increase the benefits that health care provides to them. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our?hhc?philosophy by delivering innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology. For more information about Eisai Co., Ltd., please visit?https://www.eisai.com.

 

5. About DeNA’s healthcare initiatives

With its healthcare business mission of “Staying healthy with fun”, DeNA provides healthcare services such as its gene screening service “MYCODE” and its healthcare engagement app “kencom” aimed at healthcare insurance agencies and municipalities, applying engagement science as cultivated through its gaming and sports businesses. DeNA was selected in 2019 and 2020 consecutively for the “Health and Productivity Branding”, a designation that is granted by Japan’s Ministry of Economy, Trade, and Industry in collaboration with the Tokyo Stock Exchange for companies that are evaluated to think and act strategically with an operational perspective for the health of their employees.

 

6. About DeNA Co., Ltd.

DeNA Co., Ltd.’s corporate mission is to “Delight and Impact the World”. Applying its strengths in internet and AI, DeNA aims to create various solutions for various social issues in fields ranging from entertainment, including gaming and social concerts, to an expanding sports presence, including sponsorship of the Yokohama Bay Stars baseball team, as well as in the healthcare and automotive industries. For more information about DeNA Co., Ltd., please visit?https://dena.com/intl/.

 

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

DeNA Co., Ltd.
PR Group
e-mail: [email protected]

The Alzheimer’s Clinical Trials Consortium (ACTC), Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”), and Biogen Inc. (Nasdaq: BIIB, Headquarters: Cambridge, Massachusetts, United States, CEO: Michel Vounatsos, “Biogen”) announced today that a new Phase III clinical study (AHEAD 3-45) of BAN2401, an anti-amyloid beta (Aβ) protofibril antibody, has been initiated in the United States of America for individuals with preclinical Alzheimer’s disease (AD), meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains. Currently, BAN2401 is being studied in a pivotal Phase III clinical study in symptomatic early AD (Clarity AD), following the outcome of the Phase II clinical study (Study 201). The AHEAD 3-45 will be conducted in the US, Japan, Canada, Australia, Singapore, and Europe.

AHEAD 3-45 is a Phase III clinical study, conducted as a public-private partnership between the ACTC, funded by the National Institute on Aging, part of the National Institutes of Health, and Eisai. After a common screening period in AHEAD 3-45, participants will be enrolled into one of two randomized, double-blind, placebo controlled trials based on the level of amyloid in the brain: the A45 trial and the A3 trial. A total of 1400 participants will be enrolled in the study and treated with BAN2401 for 216 weeks. The A45 trial will enroll cognitively unimpaired participants who have elevated levels of amyloid in the brain, and aims to prevent cognitive decline and suppress the progression of brain AD pathology with BAN2401 administration. The primary endpoint for A45 is the change from baseline in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment. Secondary endpoints are changes from baseline in brain amyloid levels as measured by amyloid positron emission tomography (PET) and in brain tau levels as measured by tau PET and Cognitive Function Index, a participant and study partner reported outcome. The A3 trial will enroll cognitively unimpaired participants who have an intermediate amount of amyloid in the brain, and who are at high risk for further Aβ accumulation. The primary endpoint for A3 is change from baseline in brain amyloid levels as measured by amyloid PET. The secondary endpoint is change from baseline in brain tau levels as measured by tau PET. Both trials include additional clinical assessment scales, imaging, blood biomarkers and cerebrospinal fluid (CSF) in a subset, as exploratory endpoints. An ATN (Amyloid, Tau, Neurodegeneration) biomarker panel of imaging and biofluid, especially CSF, markers including Aβ 1-42, Aβ 1-40, t-tau, p-tau, neurogranin, neurofilament light chain, will be used to evaluate therapeutic effects on the progression of AD pathophysiologic changes.

“It is hoped that initiating treatment much earlier in the disease process may be advantageous in preventing future cognitive decline. The AHEAD 3-45 should provide critically important answers about the optimal time to intervene with anti-amyloid therapy” said Dr. Reisa Sperling, Director, Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and co-Principal Investigator, ACTC.

Dr. Aisen, Director of the University of Southern California Alzheimer’s Therapeutic Research Institute, which serves as the coordinating center for the ACTC, noted, “The mission of the ACTC includes the development of public-private partnerships to conduct trials of promising candidate therapies. AHEAD 3-45 is the type of collaboration we need in the fight against Alzheimer’s disease.”

“The initiation of AHEAD 3-45 with BAN2401, focused on therapies for the earliest stages of the AD continuum through our collaboration with the ACTC group, marks an exciting time for us,” says Lynn Kramer, M.D., Chief Clinical Officer, Neurology Business Group, Eisai. “This represents a next step in developing precision therapies for AD using biomarker panels as part of our?human health care?mission; we are committed to making a difference for patients, their families, and health care professionals across the globe.”

For additional information please visit:?https:/www.a3a45.org/

BAN2401 is a humanized, monoclonal, anti- Aβ soluble aggregate (protofibril) antibody obtained through collaboration research between Eisai and BioArctic AB (Sweden). BAN2401 selectively binds to neutralize and eliminate toxic Aβ protofibrils that are thought to be a causative factor for AD. This suggests that BAN2401 may have the potential to have an effect on disease pathology and to slow the progression of AD. Study 201 demonstrated a statistically significant slowing of disease progression and decreasing of brain Aβ accumulation as the first late-stage large scale clinical study for early AD, and successfully showed potential disease-modifying effects. It is being conducted along with the 201 Open-Label Extension (OLE) study (Open-label continuous administration study) and one pivotal clinical study (Clarity AD). Eisai and Biogen Inc. have entered into a collaboration to develop and commercialize BAN2401.

[Notes to editors]

1. About The Alzheimer’s Clinical Trials Consortium (ACTC)

The ACTC, funded by the National Institute on Aging at the National Institutes of Health (grant number U24AG057437), provides the infrastructure for academic clinical trials in Alzheimer’s Disease and related dementias. The consortium, based at the University of Southern California, Harvard University and the Mayo Clinic, includes expert units to support clinical trials design, biostatistics, informatics, medical safety, regulatory oversight, recruitment, clinical operations, data management, site monitoring, a biomarker laboratory and repository, and neuroimaging. The ACTC includes 35 primary clinical sites across the United States.
2. About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. Eisai’s corporate philosophy is based on the?human health care?(hhc) concept, which is to give first thought to patients and their families, and to increase the benefits that health care provides to them. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our?hhc?philosophy by delivering innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.

Leveraging the experience gained from the development and marketing of Aricept^?, a treatment for Alzheimer’s disease and dementia with Lewy bodies, Eisai aims to establish the “Eisai Dementia Platform.” Through this platform, Eisai plans to deliver novel benefits to those living with dementia and their families through constructing a “Dementia Ecosystem,” by collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, finance, fitness clubs, automobile makers, retailers, and care facilities. For more information about Eisai Co., Ltd., please visit?https://www.eisai.com.
3. About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer’s disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.

We routinely post information that may be important to investors on our website at?https://www.biogen.com. Follow us on social media –?Twitter,?LinkedIn,?Facebook,?YouTube.
4. About the National Institutes of Health (NIH), National Institute of Aging (NIA)

NIA, one of the 27 Institutes and Centers of NIH, leads a broad scientific effort to understand the nature of aging and to extend the healthy, active years of life. NIA is the primary Federal agency supporting and conducting Alzheimer’s disease research. The National Institutes of Health, National Institute of Aging are providing funding for the A45 Study (grant number R01AG061848) and A3 Study (grant number R01AG054029)
5. About the Preclinical AD Cognitive Composite 5 (PACC5)

The PACC5 is a composite score for evaluating the severity of cognitive decline to enable highly-sensitive detection of changes in clinical functions in the preclinical AD stage.
6. About the Cognitive Function Index (CFI)

The Cognitive Function Index is an evaluation index that assesses the ability to perform advanced functional tasks in daily life and general cognitive function.

?

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 BAN2401; the potential benefits, safety, and efficacy of BAN2401; the clinical development program for BAN2401, including the AHEAD 3-45 study and the Clarity AD study; the results of the Phase II study of BAN2401; the identification and treatment of AD; the anticipated benefits and potential of Biogen’s collaboration arrangements with Eisai; the potential of Biogen’s commercial business and pipeline programs, including BAN2401; 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 trials may not be indicative of full results or results from later stage or larger scale clinical trials 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 trials; the occurrence of adverse safety events; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; risks of unexpected costs or delays; the risk of other unexpected hurdles; 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 are based on Biogen’s current beliefs and expectations and speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has launched a new fine granule formulation of its in-house-discovered antiepileptic drug (AED) Fycompa^??(perampanel hydrate) in Japan on July 6, 2020. Eisai received marketing and manufacturing approval for this formulation on January 23, 2020, and the fine granule formulation was added to Japan’s National Health Insurance drug price list on April 23 of the same year.

In Japan, it is estimated that there are approximately 1 million patients with epilepsy. While epilepsy is a disease that may occur regardless of age, it is said that incidence is particularly high in children and the elderly. This newly launched fine granule formula was developed so that even patients who have difficulty taking tablets such as children or those who have difficulties in taking tablets due to reduced swallowing ability may take this drug. Additionally, greater ability to adjust dosage to match patients’ symptoms becomes possible.

Fycompa is a first-in-class AED discovered at Eisai’s Tsukuba Research Laboratories and was developed in-house. It is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic AMPA receptors. In Japan, Fycompa is currently approved for monotherapy and adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older, as well as adjunctive treatment for primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

With the launch of this fine granule formulation in Japan, Eisai will continue to prioritize the provision of safety information. Furthermore, Eisai will pursue its mission of delivering “seizure freedom” to as many patients as possible, and seek to address the diverse needs of, as well as increasing the benefits provided to, patients with epilepsy and their families.

 

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

[Notes to editors]
1. Product Information
1)?Product name
Fycompa^??Fine Granules 1%

2)?Generic name
perampanel hydrate

3)?Indications?
??? Partial-onset seizures (including secondarily generalized seizures)
Adjunctive therapy with antiepileptic drugs for tonic-clonic seizures below in patients with epilepsy showing?inadequate response to other antiepileptic drugs

4)?Price?
Fycompa Fine Granules 1%: 1,068.90 yen per 1g containing 1% (package price: 106,890 yen)

5)?Packaging
Bottles of 100 g

6)?Product image

2. About Fycompa (perampanel hydrate)

Fycompa 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 AMPA receptors on postsynaptic membranes. Fycompa is available in drug form to be taken once daily orally at bedtime. An oral suspension formulation and tablet have been approved in the United States and Europe.

Fycompa is currently approved in more than 65 countries and territories, including Japan, the United States, China, and other countries in Europe and in Asia as adjunctive treatment for partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 12 years of age and older. In addition, Fycompa has been approved in more than 60 countries, including the United States, Japan, in Europe and in Asia for treatment as an adjunctive therapy for primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older. In Japan and the United States, Fycompa is approved for monotherapy and adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older. In Europe, an application has been submitted seeking the additional approval of Fycompa for adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) or primarily generalized tonic-clonic seizures in pediatric patients with epilepsy. To date, Fycompa has been used to treat more than 300,000 patients worldwide across all indications.

Eisai is conducting a global Phase III clinical study (Study 338) for the agent in patients with seizures associated with Lennox-Gastaut syndrome. In addition, Eisai is conducting development of an injection formulation.

 

3. About Epilepsy

Epilepsy affects approximately 1 million people in Japan, 3.4 million people in the United States, 6 million people in Europe, 9 million people in China, and approximately 60 million people worldwide. As approximately 30% of patients with epilepsy are unable to control their seizures with currently available AEDs¹, this is a disease with significant unmet medical need.

Epilepsy is broadly categorized by seizure type, with partial-onset seizures accounting for approximately 60% of epilepsy cases and generalized seizures accounting for approximately 40%. In a partial-onset seizure, an abnormal electrical disturbance occurs in a limited area of the brain, and may subsequently spread throughout the brain, becoming a generalized seizure (known as a secondarily generalized seizure). In a generalized seizure, abnormal electrical disturbances occur throughout the brain, and can be followed by a loss of consciousness or physical symptoms manifested throughout the whole body.

 

¹?“The Epilepsies and Seizures: Hope Through Research. What are the epilepsies?” National Institute of Neurological Disorders and Stroke, accessed May 24, 2016,?http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm#230253109?.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its U.S. subsidiary Eisai Inc. has launched its in-house discovered orexin receptor antagonist DAYVIGO?^?(lemborexant) CIV for the treatment of adults with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance in the U.S. on June 1, 2020.

Discovered at Eisai’s Tsukuba Research Laboratories and developed in-house, DAYVIGO is a small-molecule compound. The mechanism of action in the treatment of insomnia is presumed to be through antagonism of orexin receptors¹. The orexin neuropeptide signaling system plays a role in wakefulness¹. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R is thought to suppress wake drive. Lemborexant binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist (IC50 values of 6.1 nM and 2.6 nM, respectively).

DAYVIGO was approved in the U.S. by the U.S. Food and Drug Administration (FDA) based on findings from the lemborexant clinical development program, which included two pivotal Phase 3 studies²?(SUNRISE 1 and SUNRISE 2) in nearly 2,000 adult patients with insomnia.

SUNRISE 1 was a one month, randomized, double-blind, placebo- and active-controlled multi-center, parallel-group clinical trial in adult female subjects age 55 and older and male subjects 65 years and older who met DSM-5 (the Diagnostic and Statistical Manual of Mental Disorders – 5th edition) criteria for insomnia disorder. The primary efficacy endpoint was the mean change in latency to persistent sleep (LPS; defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness) from baseline to end of treatment (day 29/30), as measured by overnight polysomnography (PSG) monitoring. The secondary efficacy endpoints in SUNRISE 1 were the mean change from baseline to end of treatment (day 29/30) in sleep efficiency (SEF) and wake after sleep onset (WASO) measured by PSG. In SUNRISE 1, DAYVIGO 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, LPS, compared to placebo. DAYVIGO 5 mg and 10 mg demonstrated statistically significant improvement in SE and WASO compared to placebo and active-controlled.

SUNRISE 2 was a long-term (six month), randomized, double-blind, placebo-controlled, multi-center, trial in adult patients age 18 or older who met DSM-5 criteria for insomnia disorder. The primary efficacy endpoint was the mean change from baseline to end of treatment at six months for patient-reported (subjective) sleep onset latency (sSOL), defined as the estimated minutes from the time that the subject attempted to sleep until sleep onset. Pre-specified secondary efficacy endpoints for sleep maintenance were change from baseline to end of treatment at six months for patient reported sleep efficiency (sSEF; defined as the proportion of time spent asleep per time in bed) and wake after sleep onset (sWASO; defined as the minutes of wake from the onset of sleep until wake time). The pre-specified primary and secondary efficacy endpoints were measured using a Sleep Diary. In SUNRISE 2, DAYVIGO 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, sSOL, compared to placebo. DAYVIGO 5 mg and 10 mg also showed statistically significant superiority in sSEF and sWASO.¹

Analyses in both studies suggested DAYVIGO was not associated with rebound insomnia, and there was no evidence of withdrawal effects following treatment discontinuation, suggesting it does not produce physical dependence in those taking it for up to one year. DAYVIGO is the first FDA-approved insomnia medication with safety data over a 12-month treatment period and with sleep onset and sleep maintenance efficacy data over a six-month treatment period in a pivotal clinical study.

The most common adverse reaction (reported in 5% or more of patients treated with DAYVIGO and at least twice the rate of placebo) in the SUNRISE1 and SUNRISE2 (SUNRISE2 was initiated 30 days after first dosing) studies was somnolence (DAYVIGO 10 mg, 10%; DAYVIGO 5 mg, 7%; placebo, 1%).

In a special safety study (Study 106)³, DAYVIGO at 5 mg and 10 mg doses did not cause statistically significant impairment in next morning driving performance in healthy adult or elderly subjects (compared with placebo). Impairment was seen in some people taking the 10 mg dose. Patients using the 10 mg dose should be cautioned about the potential for next-morning driving impairment because there is individual variation in sensitivity to DAYVIGO. Additional special safety studies (Study 108)⁴evaluated middle-of-the-night safety, next morning postural stability and memory. The effects of Dayvigo on next day postural stability and memory were evaluated in two randomized, placebo and active-controlled trials in healthy subjects and insomnia patients age 55 and older. There were no meaningful differences between DAYVIGO and placebo on next-day postural stability or memory at either dose. Patients should be cautioned about the potential for middle-of-the-night postural instability as well as attention and memory impairment.

DAYVIGO (5 mg, 10 mg tablets) received approval from the U.S. FDA in December 2019, and was designated as a Schedule IV controlled substance by the U.S. Drug Enforcement Administration (DEA) in April 2020. According to this Schedule IV designation, individuals with a history of abuse or addiction to alcohol or other drugs may be at an increased risk for abuse and addiction to DAYVIGO and such patients should be followed carefully. Eisai received manufacturing and marketing approval for DAYVIGO as an insomnia treatment in Japan in January 2020, and was included in Japan’s National Health Insurance Drug Price List in April 2020. It is being prepared for launch in Japan. Eisai has also submitted a new drug application seeking approval of this agent for use in the treatment of insomnia in Canada in August 2019.

Insomnia is characterized by difficulty falling asleep, staying asleep, or both, despite an adequate opportunity to sleep^{5, 6}. Insomnia is one of the most common sleep-wake disorders with high prevalence. Approximately 30% of adults worldwide have symptoms of insomnia^{7, 8}, and many of them persist for months to years.

With the launch of DAYVIGO and through its continuing research and development efforts focusing on orexin biology, Eisai aspires to improve the lives of patients suffering from sleep disorders.

 

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

 

[Notes to editors]
1. About (lemborexant)
Lemborexant is Eisai’s in-house discovered and developed small molecule that binds to orexin receptors, OX1R and OX2R (IC50 values of 6.1 nM and 2.6 nM, respectively) and acts as a competitive antagonist with stronger inhibition effect to OX2R. In individuals with insomnia, it is possible that orexin signaling regulating wakefulness is not functioning normally.

The orexin neuropeptide signaling system plays a role in wakefulness.²?Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive. DAYVIGO is being prepared for launch in Japan. Eisai has also submitted a new drug application seeking approval of this agent for use in the treatment of insomnia in Canada in August 2019.

For further information on DAYVIGO in the United States, including Important Safety Information (ISI), please visit the DAYVIGO website (DAYVIGO.com).

2. About?Sleep-Wake Disorders and?Insomnia
Sleep-wake disorders consist of disease categories such as insomnia, Irregular Sleep-Wake Rhythm Disorder (ISWRD), hypersomnia and breathing-related sleep disorders. Among the sleep-wake disorders, insomnia is the most common with persistent insomnia symptoms experienced by approximately 30 percent of the adult population worldwide.^7,8?Insomnia disorder is characterized by difficulty falling asleep, staying asleep, or both, despite an adequate opportunity to sleep.^5,6

Diagnostic criteria in the U.S. for insomnia disorder include if the sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral or other important areas of functioning, occurs at least three nights per week and is present for at least three months.

Sleeping well is essential for good health⁹,?and studies suggest an optimal sleep duration between seven and eight hours.¹⁰?Poor sleep is associated with a wide range of health consequences.^5,12

Women are 1.4 times more likely than men to suffer from insomnia.¹¹?Older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent waking, and early waking, that can lead to less sleep time.¹²

3. About SUNRISE 1 (Study 304)²
SUNRISE 1 is a one-month trial in adult female patients age 55 and older and male patients 65 years and older who met DSM-5 criteria for insomnia disorder. Patients were randomized to placebo (n=208), DAYVIGO 5 mg (n=266) or 10 mg (n=269), or active comparator (n=263) once nightly. The primary efficacy endpoint was the mean change from baseline to end of treatment at Days 29/30 in latency to persistent sleep (LPS; the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness). Secondary efficacy endpoints were the mean change from baseline to end of treatment at Days 29/30 in sleep efficiency (SEF) and wake after sleep onset (WASO). These endpoints were measured by overnight polysomnography monitoring.

4. About SUNRISE 2 (Study 303)²
SUNRISE 2 is a six-month placebo-controlled treatment trial with a 6-month parallel-group extension period including adult patients age 18 or older who met DSM-5 criteria for insomnia disorder. Patients were randomized to placebo (n=325), DAYVIGO 5 mg (n=323), or DAYVIGO 10 mg (n=323) once nightly. The primary efficacy endpoint was the mean change from baseline to end of treatment at six months for subjective sleep onset latency (sSOL; the estimated minutes from the time that the patient attempted to sleep until sleep onset). Secondary efficacy endpoints were mean change from baseline to end of treatment at six months subjective sleep efficiency (sSEF; the proportion of time spent asleep per time in bed) and wake after sleep onset (sWASO; the minutes of wake from the onset of sleep until wake time). These endpoints were measured by sleep diary.

5. About Study 106³
Study 106 was a randomized, double-blind, placebo- and active-controlled, four period, crossover Phase I study to evaluate the effect of lemborexant in 48 healthy adults and elderly volunteers (23 to 58 years of age, mean: 58.5 years old) to evaluate on-road driving performance. Volunteers (65 years and older: 24, 23 to 64 years old: 24) were treated at bedtime with two out of three dose levels of lemborexant (2.5, 5 or 10 mg) and placebo for eight consecutive days. Zopiclone 7.5 mg as an active control was administered on days one and eight only, with placebo given for the six days in between. The primary endpoint was to evaluate change of standard deviation of lateral position (SDLP) during an on-road driving test conducted after the first (in the morning of Day 2) and last day (in the morning of Day 9) of treatment administration after 9-hour dose.

In the on-road test, the volunteers drove a specially instrumented vehicle for about one hour over 100km (approximately 60 miles) primary highway circuit, accompanied by a licensed driving instructor. The task was to drive with a steady lateral position between the delineated boundaries of the slower traffic lane, while maintaining a constant speed of 95km/h.

Although lemborexant at doses of 5 mg and 10 mg did not cause statistically significant impairment in next-morning driving performance in adult or elderly subjects (compared with placebo), driving ability was impaired in some subjects taking 10 mg lemborexant.

6. About Study 108⁴
Study 108 was a randomized, double-blind, four period crossover Phase I study to evaluate the effect of lemborexant on postural stability, auditory awakening threshold, and cognitive performance in 56 healthy volunteers 55 years and older. Participants were treated at bedtime with a single dose of placebo, lemborexant 5 mg, lemborexant 10 mg, or active control. There was a statistically significant increase in body sway for both doses of lemborexant compared with placebo. The next morning, shortly after the end of eight hours in bed neither dose of lemborexant had statistically significant residual effects on this measure of postural stability as compared to placebo.
References
¹?Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities.?Annu Rev Pharmacol Toxicol. 2011;51:243‐266.
²?Eisai Inc. DAYVIGO Full Prescribing Information. 2020.
³?Vermeeren A, et al. On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers.?Sleep.?2019 42 (4): zsy260.
⁴?Murphy P, et al. Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening,?J. Clinical Sleep Medicine.?2020: 16(5):765-773.
⁵?Institute of Medicine. Sleep disorders and sleep deprivation: An unmet public health problem. Washington, DC: National Academies Press. 2006.
⁶?Ohayon MM, et al. Epidemiology of insomnia: what we know and what we still need to learn.?Sleep Med Rev.?2002;6(2):97-111.
⁷?Ferrie JE, et al. Sleep epidemiology – a rapidly growing field. Int J Epidemiol.2011;40(6):1431–1437.
⁸?Roth T. Insomnia: definition, prevalence, etiology and consequences.?J Clin Sleep Med. 2007;3(5 Suppl):S7–S10.
⁹?Cappuccio FP, et al.?Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies.?Sleep.?2010;33(5):585-592.
¹⁰?Pase MP, Himali JJ, Grima NA, et al. Sleep architecture and the risk of incident dementia in the community.??Neurology.?2017;89(12):1244-1250.
¹¹?Roth T, et al. Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, tenth revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, second edition criteria: results from the America Insomnia Survey. Biol Psychiatry.?2011;69:592– 600.
¹²?Crowley K.?Sleep and sleep disorders in older adults.?Neuropsychol Rev. 2011;21(1):41-53.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that presentations on a series of abstracts regarding its in-house discovered lenvatinib mesylate (multikinase inhibitor, product name: LENVIMA^?, “l(fā)envatinib”) and eribulin mesylate (halichondrin class microtubule dynamics inhibitor, product name: HALAVEN^?, “eribulin”) will be given at the American Society of Clinical Oncology (ASCO20 Virtual Scientific Program*), from May 29 to 31, 2020.
* Presentation materials will be made available on demand via ASCO’s website at 8:00 AM on May 29^th?(ET).

At this year’s meeting, the final results of two studies will be presented on the combination therapy of lenvatinib with the anti-PD-1 antibody KEYTRUDA^??(generic name: pembrolizumab, “pembrolizumab”) from Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada). One is the oral presentation of the metastatic renal cell carcinoma cohort (Abstract number: 5008) of Study 111 / KEYNOTE-146, and the other is the poster discussion presentation of the first-line therapy for unresectable hepatocellular carcinoma (Abstract number: 4519) in Study 116 / KEYNOTE-524**.
**This release discusses investigational compounds and investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds and investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib.

Eisai positions oncology as a key franchise area and aims to create innovative drugs that act towards?curing cancer. Eisai will continue to create innovation in the development of new drugs based on cutting-edge cancer research, and aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals.