WOODCLIFF LAKE, N.J., July 24, 2020 /PRNewswire/ -- Eisai Inc., the U.S. pharmaceutical subsidiary of Eisai Co., Ltd., announced today the presentation of new data and information from the company's robust AD pipeline, including BAN2401 and lemborexant. This data will be among nine abstracts communicated in one oral and eight poster presentations at the virtual Alzheimer's Association International Conference (AAIC), July 27-31, 2020.

"Eisai has a compelling track record of trailblazing in the field of Alzheimer's disease and dementia. The breadth of information Eisai will present demonstrates our continued dedication to bring patients therapies for Alzheimer's disease and its symptoms as soon as possible," said Harald Hampel, MD, Vice President, Chief Medical Officer, Neurology Business Group, Eisai Inc. "We look forward to sharing data and discussing the scientific rationale that the amyloid pathway plays a key role in the pathophysiology of Alzheimer's disease as well as the latest developments in biomarkers."

Eisai and Biogen Joint Investigational Assets

Eisai Presentations for BAN2401:

• Study design for the Phase 3 AHEAD 3-45 trial of BAN2401 in patients with early AD will be communicated as an oral presentation on July 29. 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. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium, funded by the National Institute on Aging, part of the National Institutes of Health, and Eisai.
• Preliminary analysis of Amyloid Related Imaging Abnormalities – Edema/Effusion (ARIA-E) rates. These results will be presented on July 29.
• Preliminary assessment of BAN2401-mediated amyloid reduction for the 10 mg/kg bi-weekly dose of BAN2401 from the 18-month Phase 2b study BAN2401-G000-201 open-label extension study. These results will be presented on July 29.

Biogen Presentation for Aducanumab:

• Biogen will share an encore platform presentation of the previously reported topline results from the aducanumab Phase 3 EMERGE and ENGAGE studies. No new data from the studies are included in the encore presentation, which will be pre-recorded and followed by an online question and answer (Q&A) session.

Additional Eisai AAIC Conference Highlights

A satellite symposium and additional studies will further explore key topics affecting AD patients.

• An Eisai-sponsored virtual satellite symposium titled, "The Development of the A/T/N/x Classification System for Different Contexts of Use across the Alzheimer's Disease Continuum: State-of-the-Art and Future Perspectives for Clinical Practice and Therapy Development," will be available on-demand throughout the duration of the virtual program and up to a month following the conference conclusion.
   
  The A/T/N system is an unbiased descriptive classification scheme for AD biomarkers using core AD pathophysiological mechanisms (amyloid-β (A), tau (T) and neurodegeneration (N)). The A/T/N/x system has the potential to guide AD therapy development and clinical practice for a precision medicine-oriented approach. The symposium will provide a state-of-the-art A/T/N/x classification system across the AD continuum, including main challenges in the validation and qualification process for different contexts of use. Featured speakers will include:
  • Jeffrey Cummings, MD, ScD, Director, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, UNLV, Founding Director, Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic
  • Clifford R. Jack, Jr., MD
  • Kaj Blennow, MD, PhD, Professor and Academic Chair in Clinical Neurochemistry, Head of the Clinical Neurochemistry Lab, Sahlgrenska University Hospital, University of Gothenberg
• Additional studies covering the patient, caregiver and economic burden of AD and its effect on daily living and quality of life will be presented in a series of poster presentations.
• Long-term safety and efficacy data from a Phase 2 extension study of lemborexant in patients with irregular sleep-wake rhythm disorder (ISWRD) and AD dementia will also be presented as a poster presentation. Lemborexant was approved in December 2020 by the U.S. Food and Drug Administration for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.¹ Lemborexant is contraindicated in patients with narcolepsy.

"In addition to a robust pipeline of potential disease-modifying compounds targeting Alzheimer's pathological hallmarks of amyloid, tau and neurodegeneration, Eisai is researching other novel therapies aiming to treat both the disease and the clinical symptoms of Alzheimer's disease, such as cognition and sleep disorders," said Ivan Cheung, Chairman, Eisai Inc and Global President, Neurology Business Group, Eisai Co., Ltd. "With our partner Biogen's filing of the aducanumab Biologics License Application with the U.S. FDA, the initiation of the BAN2401 Phase 3 AHEAD 3-45 clinical study and the data presented at this year's AAIC, it is an incredibly exciting time for Eisai's growing Alzheimer's disease franchise."

The full list of Eisai and one Biogen (aducanumab) virtual presentations is included below. All presentations will be available on demand via the AAIC website approximately one month post-conference to registered participants. There is no charge to register for this year's event.

AAIC 2020 Presentations

Biogen AAIC 2020 Presentations

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

[Notes to editors]

1.  About Aducanumab
Aducanumab (BIIB037) is an investigational human monoclonal antibody studied for the treatment of AD. Based on clinical data, aducanumab has the potential to impact underlying disease pathophysiology, slow cognitive and functional decline and provide benefits on patients' ability to perform activities of daily living, including conducting personal finances, performing household chores, such as cleaning, shopping and doing laundry, and independently traveling out of the home. If approved, aducanumab would be the first treatment to meaningfully change the course of the disease for individuals living with Alzheimer's.

2.  About BAN2401
BAN2401 is an investigational humanized monoclonal antibody for Alzheimer's disease that is the result of a strategic research alliance between Eisai and BioArctic. BAN2401 selectively binds to neutralize and eliminate soluble, toxic Aβ aggregates (protofibril) that are thought to contribute to the neurodegenerative process in AD. As such, BAN2401 may have the potential to have an effect on disease pathology and to slow down the progression of the disease. Eisai obtained the global rights to study, develop, manufacture and market BAN2401 for the treatment of AD pursuant to an agreement concluded with BioArctic in December 2007. In March 2014, Eisai and Biogen entered into a joint development and commercialization agreement for BAN2401 and the parties amended that agreement in October 2017.

Currently, BAN2401 is being studied in a pivotal Phase 3 clinical study in symptomatic early AD (Clarity AD), following the outcome of the Phase II clinical study (Study 201). In July of 2020, the Phase III 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, was initiated. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium, funded by the National Institute on Aging, part of the National Institutes of Health, and Eisai.

3.  About the Joint Development between Eisai and Biogen for Alzheimer's Disease
Eisai and Biogen are collaborating on the joint development and commercialization of AD treatments. Biogen serves as the lead in the co-development of aducanumab and Eisai serves as the lead in the co-development of BAN2401, anti-amyloid beta (Aβ) protofibril antibodies, and the companies plan to pursue marketing authorizations for aducanumab and BAN2401 worldwide. If approved, the companies will also co-promote aducanumab and BAN2401 in major markets, such as the United States, the European Union and Japan. Both companies will equally split overall costs, including research and development expenses. Eisai will book all sales for BAN2401 following marketing approval and launch, and profits will be equally shared between the companies.

4.  About the Collaboration between Eisai and BioArctic for Alzheimer's Disease
Since 2005, BioArctic has had a long-term collaboration with Eisai regarding the development and commercialization of drugs for the treatment of AD. The commercialization agreement on the BAN2401 antibody was signed in December 2007, and the development and commercialization agreement on the antibody BAN2401 back-up for AD, which was signed in May 2015. Eisai is responsible for the clinical development, application for market approval and commercialization of the products for AD. BioArctic has no development costs for BAN2401 in AD.

5.  About Lemborexant
Lemborexant is a small-molecule compound, discovered and developed by Eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2). In individuals with normal daily sleep-wake rhythms, orexin signaling is believed to promote periods of wakefulness.² In individuals with insomnia, it is possible that orexin signaling regulating wakefulness is not functioning normally.

INDICATION

DAYVIGO (lemborexant) is an orexin receptor antagonist indicated for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.¹

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• DAYVIGO is contraindicated in patients with narcolepsy.

WARNINGS AND PRECAUTIONS

• Central Nervous System (CNS) Depressant Effects and Daytime Impairment:
  DAYVIGO can impair daytime wakefulness. CNS depressant effects may persist in some patients up to several days after discontinuing DAYVIGO. Prescribers should advise patients about the potential for next-day somnolence.
   
  Driving ability was impaired in some subjects taking DAYVIGO 10 mg. Risk of daytime impairment is increased if DAYVIGO is taken with less than a full night of sleep remaining or at a higher than recommended dose. If taken in these circumstances, patients should not drive or engage in activities requiring mental alertness.
   
  Use with other classes of CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment. Dosage adjustments of DAYVIGO and concomitant CNS depressants may be necessary when administered together. Use of DAYVIGO with other insomnia drugs is not recommended. Patients should be advised not to consume alcohol in combination with DAYVIGO.
   
  Because DAYVIGO can cause drowsiness, patients, particularly the elderly, are at a higher risk of falls.
   
• Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-Like Symptoms:
  Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions can occur with DAYVIGO. Prescribers should explain these events to patients.
   
  Symptoms similar to mild cataplexy can occur with DAYVIGO and can include periods of leg weakness lasting from seconds to a few minutes, can occur either at night or during the day, and may not be associated with identified triggering event (e.g., laughter or surprise).
   
• Complex Sleep Behaviors:
  Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (e.g., preparing and eating food, making phone calls, having sex), have been reported to occur with the use of hypnotics such as DAYVIGO. Events can occur in hypnotic-naïve and hypnotic-experienced persons. Patients usually do not remember these events. Complex sleep behaviors may occur following the first or any subsequent use of DAYVIGO, with or without the concomitant use of alcohol and other CNS depressants. Discontinue DAYVIGO immediately if a patient experiences a complex sleep behavior.
   
• Patients with Compromised Respiratory Function:
  The effect of DAYVIGO on respiratory function should be considered for patients with compromised respiratory function. DAYVIGO has not been studied in patients with moderate to severe obstructive sleep apnea (OSA) or chronic obstructive pulmonary disease (COPD).
   
• Worsening of Depression/Suicidal Ideation:
  Incidence of suicidal ideation or suicidal behavior, as assessed by questionnaire, was higher in patients receiving DAYVIGO than placebo (0.3% for DAYVIGO 10 mg, 0.4% for DAYVIGO 5 mg, and 0.2% for placebo).
   
  In primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions (including completed suicides) have been reported. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdose is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed at any one time.
   
  The emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
   
• Need to Evaluate for Comorbid Diagnoses:
  Treatment of insomnia should be initiated only after careful evaluation of the patient. Reevaluate for comorbid conditions if insomnia persists or worsens after 7 to 10 days of treatment. Worsening of insomnia or the emergence of new cognitive or behavioral abnormalities may be the result of an unrecognized underlying psychiatric or medical disorder and can emerge during the course of treatment with sleep-promoting drugs such as DAYVIGO.

ADVERSE REACTIONS

• The most common adverse reaction (reported in 5% of patients treated with DAYVIGO and at least twice the rate of placebo) with DAYVIGO was somnolence (10% for DAYVIGO 10 mg, 7% for DAYVIGO 5 mg, 1% for placebo).

DRUG INTERACTIONS

• CYP3A Inhibitors: The maximum recommended dose of DAYVIGO is 5 mg no more than once per night when co-administered with weak CYP3A inhibitors. Avoid concomitant use of DAYVIGO with strong or moderate CYP3A inhibitors.
   
• CYP3A Inducers: Avoid concomitant use of DAYVIGO with moderate or strong CYP3A inducers.

USE IN SPECIFIC POPULATIONS

• Pregnancy and Lactation: There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to DAYVIGO during pregnancy.
   
  Healthcare providers are encouraged to register patients in the DAYVIGO pregnancy registry by calling 1-888-274-2378. There are no available data on DAYVIGO use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
   
  There are no data on the presence of lemborexant in human milk, the effects on the breastfed infant, or the effects on milk production. Infants exposed to DAYVIGO through breastmilk should be monitored for excess sedation.
   
• Geriatric Use: Exercise caution when using doses higher than 5 mg in patients ≥65 years old.
   
• Renal Impairment: Patients with severe renal impairment may experience an increased risk of somnolence.
   
• Hepatic Impairment: The maximum recommended dose of DAYVIGO is 5 mg in patients with moderate hepatic impairment. DAYVIGO is not recommended in patients with severe hepatic impairment. Patients with mild hepatic impairment may experience an increased risk of somnolence.

DRUG ABUSE AND DEPENDENCE

• DAYVIGO is a Schedule IV-controlled substance.
• Because individuals with a history of abuse or addiction to alcohol or other drugs may be at increased risk for abuse and addiction to DAYVIGO, follow such patients carefully.

For more information about DAYVIGO, see full Prescribing Information.

6.  About Elenbecestat
Elenbecestat is Eisai's in-house discovered and developed BACE (beta-site amyloid precursor protein cleaving enzyme) inhibitor. Phase 3 clinical studies (MISSION AD1, AD2) for elenbecestat aimed at early AD were discontinued in September 2019.

7.  About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.

Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US and follow us on Twitter and LinkedIn.

References
¹ Eisai Inc. DAYVIGO Full Prescribing Information. 2020.
² Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2011;51:243–266.

Contact:

Eisai Inc.
Libby Holman
201-753-1945
libby_holman@eisai.com       

SOURCE Eisai Inc.