NUTLEY, N.J., March 31, 2022 /PRNewswire/ -- Eisai Inc., the U.S. pharmaceutical subsidiary of Eisai Co., Ltd., announced today the company will present research from its robust neurology portfolio, including the findings on lecanemab, an investigational anti-amyloid beta (Aβ) protofibril antibody being developed for the treatment of early Alzheimer's disease (AD) at the American Academy of Neurology^® (AAN), occurring in Seattle, Washington April 2-7, 2022, with virtual sessions April 24-26, 2022. Research findings from lecanemab, the insomnia dual orexin receptor antagonist DAYVIGO^® (lemborexant) CIV and the antiepileptic medication FYCOMPA^® (perampanel) CIII will be featured in 10 presentations.

"Eisai is pleased to share research for our broad neurology portfolio targeting both the pathophysiology and the clinical symptoms of neurological diseases," said Michael Irizarry, M.D., Senior Vice President, Deputy Chief Clinical Officer, Neurology Business Group, Eisai Inc. "We will present exciting data from the early Alzheimer's disease Phase 2b core and open-label extension study showing lecanemab's clearance of amyloid-beta plaque from the brain, which is correlated with plasma biomarkers and clinical outcomes, and amyloid-related imaging abnormality rates. Eisai aims to bring potential innovations to people living with neurological disorders and health care providers as quickly as possible as we work to fulfill our human health care mission."

• Lecanemab: An Assessment of the Clinical Effects, the Correlation of Plasma Aβ 42/40 Ratio with Changes in Brain Amyloid PET SUVr, and Safety from the Core and Open Label Extension of the Phase 2 Proof-of-Concept Study, BAN2401-G000-201, in Subjects with Early Alzheimer's Disease (AD) – Data from the Phase 2b Core and open-label extension (OLE) study will be presented for lecanemab, including reduction of amyloid-plaque, longitudinal plasma Aβ 42/40 ratio (C2N PrecivityAD assay) and the relationship to longitudinal amyloid PET in the core, gap period, and OLE. This study design provided the opportunity to explore the biomarker and clinical effects of stopping and restarting lecanemab across five years of disease trajectory. This data has been shared at prior medical congresses.
• ELEVATE Study 410: Phase IV Study of Perampanel as Monotherapy or First Adjunctive Therapy in Patients Aged ≥4 Years with Focal-Onset Seizures (FOS) or Generalized Tonic-Clonic Seizures (GTCS) – Presented will be the results from a final analysis of ELEVATE (study 410), a multicenter, open-label Phase IV study evaluating FYCOMPA as a monotherapy or first adjunctive therapy in epilepsy patients aged four years and older with focal onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS) examining the primary endpoint of retention rate and secondary endpoints of seizure-freedom rate and safety. This data has been shared at prior medical congresses.
• An Assessment of Wake Bouts in Adults with Insomnia Treated with Lemborexant or Zolpidem – This presentation will evaluate the effect of lemborexant on the frequency and duration of wake bouts. Compared with placebo and zolpidem, lemborexant treatment decreased the number and time spent in long wake bouts, thereby decreasing wake time after sleep onset. This data has been shared at prior medical congresses.

Eisai considers neurology a therapeutic area of focus. Using a disciplined, pathophysiology-guided R&D approach, we are researching and developing preventative and curative treatments that will hopefully transform the lives of people impacted by neurodegenerative diseases.

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

Eisai Presentations

[Notes to editors]

1. About Lecanemab (development code: BAN2401)
Lecanemab is an investigational humanized monoclonal antibody for Alzheimer's disease (AD) that is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab selectively binds to neutralize and eliminate soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils) that are thought to contribute to the neurodegenerative process in AD. As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease. Currently, lecanemab is being developed as the only anti- Aβ antibody that can be used for the treatment of early AD without the need for titration. With regard to the results from pre-specified analysis at 18 months of treatment, Study 201 demonstrated reduction of brain Aβ accumulation (P<0.0001) and slowing of disease progression measured by ADCOMS* (P<0.05) in early AD patients. The study did not achieve its primary outcome measure** at 12 months of treatment. The Study 201 open-label extension was initiated after completion of the Core period and a Gap period off treatment of 9-59 months (average of 24 months, n=180 from core study enrolled) to evaluate safety and efficacy, and is underway.

Currently, lecanemab is being studied in a confirmatory Phase 3 clinical study in symptomatic early AD (Clarity-AD), following the outcome of the Phase 2 clinical study (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 Alzheimer's disease (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. In this clinical study, lecanemab has been selected as the background anti-amyloid therapy. Furthermore, Eisai has initiated a lecanemab subcutaneous dosing Phase 1 study. Eisai obtained the global rights to study, develop, manufacture and market lecanemab 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 lecanemab and the parties amended that agreement in March 2022.

*Developed by Eisai, ADCOMS (AD Composite Score) combines items from the ADAS-Cog (AD Assessment Scale-cognitive subscale), Clinical Dementia Rating (CDR) and the MMSE (Mini-Mental State Examination) scales to enable a sensitive detection of changes in clinical functions of early AD symptoms and changes in memory. The ADCOMS scale ranges from a score of 0.00 to 1.97, with higher score indicating greater impairment.

**An 80% or higher estimated probability of demonstrating 25% or greater slowing in clinical decline at 12 months treatment measured by ADCOMS from baseline compared to placebo.

2. About Lemborexant (product name: DAYVIGO)
Lemborexant, an orexin receptor antagonist, is Eisai's in-house discovered and developed small molecule that inhibits orexin neurotransmission by binding competitively to the two subtypes of orexin receptors (orexin receptor 1 and 2). Faster on/off receptor kinetics of lemborexant to orexin receptor 2, which suppresses both non-REM and REM sleep, may influence lemborexant's potential to facilitate improvements in sleep onset and maintenance. In June 2020, lemborexant was launched under the product name DAYVIGO in the U.S. for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance; and in July 2020, it was launched under the product name DAYVIGO in Canada and Japan for the treatment of insomnia. Eisai has submitted new drug applications seeking approval of DAYVIGO in Asian countries and others.

3. About Perampanel (product name: FYCOMPA)
FYCOMPA is a prescription medicine used in people with epilepsy aged 4 and older alone or with other medicines to treat partial-onset seizures with or without secondarily generalized seizures, and with other medicines to treat primary generalized tonic-clonic seizures for people with epilepsy aged 12 and older.

FYCOMPA, a unique oral medication, is a selective, non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist. The precise mechanism by which FYCOMPA exerts its antiepileptic effects in humans is unknown. In a pharmacokinetic study, it has been demonstrated that because of its long half life, a missed dose of FYCOMPA does not significantly impact plasma levels.

FYCOMPA is supplied as 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg film-coated tablets, and as a 0.5 mg/mL oral suspension formulation. FYCOMPA has been designated by the U.S. Drug Enforcement Administration as a federally-controlled substance (CIII). To date, FYCOMPA has been approved in more than 70 countries and territories and has been used to treat more than 410,000 patients worldwide across all indications.

4 About the Collaboration between Eisai and Biogen for Alzheimer's Disease
Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.

5. 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 lecanemab antibody was signed in December 2007, and the development and commercialization agreement on the antibody lecanemab 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 lecanemab in AD.

6. About Eisai Inc.
At Eisai Inc., human health care (hhc) is our mission and is the shared purpose that connects us to those we serve creating a network of powerful relationships that enables us to identify, understand and work to address the needs of people throughout their lives. We boldly push past the boundaries of science and aim to deliver life-changing therapies and health-related solutions that matter to people and society. We bring together science, technology and real-world expertise to pursue a world free from cancer, Alzheimer's disease and other neurodegenerative diseases. 

Everything we do is guided by the simple principle that patients and their families come first, and we have a responsibility to listen to and learn from them.

Eisai Inc. is the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd. The company's presence in the U.S. includes three discovery centers as well as commercial, clinical development and global demand organizations. To learn more about Eisai, please visit us at www.eisai.com/US and follow us on Twitter and LinkedIn. For more information on our work in neurology, please visit the Eisai U.S. Neurology LinkedIn page.

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.

DAYVIGO is contraindicated in patients with narcolepsy.

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.

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).

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.

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.

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. 

FYCOMPA^® (perampanel) is indicated in patients with epilepsy aged 4 years and older for partial-onset seizures (POS) with or without secondarily generalized seizures and adjunctive therapy for patients aged 12 years and older for primary generalized tonic-clonic (PGTC) seizures.

In the partial-onset seizures clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. These effects in FYCOMPA-treated patients led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Patients taking FYCOMPA should avoid the use of alcohol. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least one month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic (PGTC) seizure clinical trial.

Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients. Anyone considering prescribing FYCOMPA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, their caregivers, and families should be informed of the risk and advised to monitor and immediately report the emergence or worsening of depression, suicidal thoughts or behavior, thoughts about self-harm and/or any unusual changes in mood or behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. Dizziness and vertigo were reported in 35% and 47% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial.

FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 7% of placebo-treated patients. Fatigue-related events were reported in 12% and 15% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 5% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial. Patients should be advised against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known. Patients should be carefully observed for signs of central nervous system (CNS) depression when FYCOMPA is used with other drugs with sedative properties because of potential additive effects.

Falls were reported in 5% and 10% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients.

DRESS, also known as multiorgan hypersensitivity, has been reported in patients taking AEDs, including FYCOMPA. DRESS may be fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement. If signs or symptoms are present, immediately evaluate the patient and discontinue FYCOMPA if an alternative etiology for signs or symptoms cannot be established.

A gradual withdrawal is generally recommended with AEDs to minimize the potential of increased seizure frequency, but if withdrawal is a response to adverse events, prompt withdrawal can be considered.

The most common adverse reactions in patients aged 12 years and older receiving FYCOMPA (≥5% and ≥1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety. Adverse reactions in patients aged 4 to <12 years were generally similar to patients aged 12 years and older.

FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of perampanel were decreased when administered with known moderate and strong CYP3A4 inducers, including, carbamazepine, phenytoin, or oxcarbazepine. Multiple dosing of FYCOMPA 12 mg per day enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants.

Physicians are advised to recommend that pregnant patients taking FYCOMPA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Caution should be exercised when FYCOMPA is administered to pregnant or nursing women as there are no adequate data on the developmental risk associated with use in pregnant women, and no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production.

Use in patients with severe hepatic or severe renal impairment is not recommended. Dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Use with caution in patients with moderate renal impairment.

FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence and withdrawal symptoms including anxiety, nervousness, irritability, fatigue, asthenia, mood swings, and insomnia.

Please see full Prescribing Information, including Boxed WARNING.

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SOURCE Eisai Inc.