Eisai Presents Breadth of Data Across Neurology Portfolio, Including Alzheimer's Disease, Insomnia and Epilepsy
Twenty-one presentations featuring data and information on investigational lecanemab in early Alzheimer's disease, DAYVIGO® (lemborexant) CIV in insomnia, FYCOMPA® (perampanel) CIII in epilepsy and investigational lorcaserin in Dravet Syndrome

WOODCLIFF LAKE, N.J., April 16, 2021 /PRNewswire/ -- Eisai Inc., the U.S. pharmaceutical subsidiary of Eisai Co., Ltd., announced today that data from the company's deep neurology pipeline and portfolio, including Alzheimer's disease, insomnia and epilepsy, will be presented at the 73rd Annual Meeting of the American Academy of Neurology (AAN), taking place virtually from April 17-22, 2021.

"Eisai is dedicated to advancing our marketed products and robust pipeline of investigational therapies targeting disease pathophysiology as well as clinical symptoms of neurological diseases," said Ivan Cheung, Chairman, Eisai Inc. and Global President, Neurology Business Group, Eisai Co., Ltd. "With Eisai's and Biogen's joint asset, aducanumab, under regulatory review in the U.S., European Union and Japan, the companies' joint asset, lecanemab, in Phase 3 Clarity-AD and AHEAD 3-45 clinical studies and the data presented at this year's AAN, it is an incredibly exciting time for Eisai's growing Alzheimer's disease franchise and neurology portfolio." 

Eisai and Biogen Joint Investigational Assets

Lecanemab
Jointly developed by Eisai and Biogen Inc., lecanemab is an investigational humanized monoclonal antibody that binds to neutralize and eliminate soluble, toxic amyloid beta (Aβ) aggregates (protofibrils) that are thought to contribute to the neurodegenerative process in AD.

Eisai Oral Presentation for Lecanemab:

  • Lecanemab has previously demonstrated dose-dependent reductions in brain amyloid among patients with early AD in an 18-month Phase 2 study.[i] Preliminary findings from the ongoing open-label extension of this study will evaluate the effects of lecanemab on brain amyloid and ARIA-E over 12 months of treatment. These results will be presented on April 20.

Eisai Assets

Insomnia
DAYVIGO (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. In individuals with insomnia, it is possible that orexin signaling regulating wakefulness is not functioning normally.

Eisai Poster Presentations for DAYVIGO:

  • Five posters with DAYVIGO data will be presented, including analyses of its effect on a range of sleep measures and patient-reported outcomes.

Epilepsy
Fycompa is a first-in-class antiepileptic drug (AED) discovered at Eisai's Tsukuba Research Laboratories and was developed in-house. It is a noncompetitive AMPA receptor antagonist that is thought to block glutamate activity at postsynaptic AMPA receptors to reduce neuronal hyperexcitation associated with seizures.

Eisai Poster Presentations for FYCOMPA:

  • Eisai will also present seizure freedom rates for FYCOMPA monotherapy in the treatment of partial-onset seizures (POS) in Study 342, evaluating the efficacy of maintenance treatment in patients with or without earlier responses to titration in a post-hoc analysis of Study 342 (FREEDOM).
  • In addition, Eisai will present a key post hoc analysis of study 311 examining long-term seizure freedom with adjunctive FYCOMPA in pediatric epilepsy patients with POS or primary generalized tonic-clonic seizures (PGTC), as well as data on real-world clinical care.

Following consultation with the U.S. Food and Drug Administration (FDA), Eisai has initiated a Phase 3 clinical trial called MOMENTUM 1 to evaluate investigational lorcaserin as a potential treatment for Dravet Syndrome. Lorcaserin is a selective agonist (activator) of 5-HT2c, a protein receptor for the neurotransmitter serotonin. It is believed that activating this receptor may increase GABA-mediated inhibition and result in reduced seizure activity in Dravet Syndrome patients.ii

Eisai Poster Presentation for lorcaserin:

  • The lorcaserin poster will provide an overview of the study design to evaluate adjunctive lorcaserin as a potential therapy in Dravet Syndrome, a rare form of epilepsy that is often resistant to seizure medications and begins in infancy, causing frequent, prolonged seizures.iii

"Neurology has been a long-standing, key therapeutic focus area for Eisai and we are committed to the discovery and development of transformative therapies and solutions that may make a difference for patients living with Alzheimer's disease, insomnia and epilepsy," said Michael Irizarry, M.D., Vice President, Deputy Chief Clinical Officer, Neurology Business Group, Eisai Inc. "We look forward to sharing data on our investigational therapy, lecanemab, and its potential impact on brain amyloid in patients with early Alzheimer's disease."

The full list of virtual presentations is included below. All presentations will be available to registered participants via the AAN 2021 virtual platform from the start of the meeting; session recordings will be available for 30 days after the end of the conference.

AAN 2021 Presentations

Alzheimer's Disease

Topic, Session, Time (ET)

Title, Presenter

Lecanemab (BAN2401)

Scientific Platform Session 19 (S19): Aging and Dementia

Oral presentation #001

Tuesday, April 20

2:00 PM

Preliminary Analysis of BAN2401 Effects on Brain Amyloid and ARIA-E Findings Over 12 Months of Treatment in the Open-Label Extension of the Phase 2b Study BAN2401-G000-201 in Subjects With Early Alzheimer's Disease

Presenter: Dr. Chad Swanson

Lecanemab (BAN2401)

Aging, Dementia, Cognitive, and Behavioral Neurology

Poster presentation (on demand)
#3021/Abstract #017

Baseline Characteristics for Clarity AD: A Phase 3 Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study Evaluating BAN2401 in Early Alzheimer's Disease

Authors: Dr. Shau Yu Lynch, et al

Biogen Presentation for Aducanumab (Joint Investigational)

Topic, Session, Time (ET)

Title, Presenter

Aging, Dementia, Cognitive, and Behavioral Neurology

Poster presentation (on demand)

Abstract # 013

EMBARK: A Phase 3b, Open-Label, Single-Arm, Safety Study to Evaluate the Long-Term Safety and Efficacy of Aducanumab in Eligible Participants with Alzheimer's Disease

Authors: Dr. Carmen Castrillo-Viguera, et al

Insomnia

Topic, Session, Time (ET)

Title, Presenter

Lemborexant

Sleep

Poster presentation (on demand)

Abstract #005

Insomnia Treatments and On-the-road Driving Performance: A Systematic Literature Review

Authors: Dr. Genevieve Meier, et al

Lemborexant

Sleep

Poster presentation (on demand)

Abstract #007

Evaluation of Next-Dose Transition from Zolpidem to Lemborexant for the Treatment of Insomnia: A Multicenter Open-label Pilot Study

Authors: Dr. Russell Rosenberg, et al

Lemborexant

Sleep

Poster presentation

Abstract #008

Tuesday, April 20

1:00 PM – 2:00 PM

Effect of Lemborexant on Fatigue Severity and Sleep Outcomes Over 12 Months in Subjects With Clinically Significant Fatigue at Baseline

Authors: Dr. Rakeh Jain, et al

Lemborexant

Sleep

Poster presentation

Abstract #009

Tuesday, April 20

3:00 PM – 3:30 PM

Responder Profiles Over 12 Months for Sleep Onset and Sleep Maintenance Outcomes with Lemborexant

Authors: Dr. Gary Zammit, et al

Lemborexant

Sleep

Poster presentation

Abstract #010

Tuesday, April 20

2:00 PM – 3:00 PM

Effect of Lemborexant on Patient-Reported Distress About Sleeping and Interference with Daily Functioning in Subjects With Insomnia

Authors: Dr. Craig Chepke, et al

Epilepsy

Topic, Session, Time (EDT)

Title, Presenter

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #008

Perampanel Monotherapy Beyond Initial Titration to Achieve Seizure Freedom in Patients with Partial-Onset Seizures (POS), with/without Secondarily Generalized Seizures (SGS): Post Hoc Analysis of Phase III Study 342 (FREEDOM)

Authors: Dr. Ryan Husni, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #009

Tuesday, April 20

5:00 AM – 8:00 AM

Long-term Evaluation of Adjunctive Perampanel on Mental Health in Pediatric Patients with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) in Study 311

Authors: Dr. Rohit Shankar, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #010

Long-Term (1-Year) Seizure Freedom with Adjunctive Perampanel in Pediatric Patients (Aged 4–<12 Years) with Partial-Onset Seizures (POS) or Primary Generalized Tonic-Clonic Seizures (PGTCS): Post Hoc Analysis of Study 311

Authors: Dr. Robert Flamini, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #001

PROVE Study 506: Analysis of a Retrospective, Phase IV Study of Perampanel in Real-World Clinical Care of Patients Based on Study Site Participation in Previous Clinical Trials

Authors: Dr. Robert T. Wechsler, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #019

Wednesday, April 21

8:00 AM – 12:00 PM

Efficacy and Safety of Adjunctive Perampanel for Myoclonic and Absence Seizures: Post Hoc Pooled Analysis of Adult, Adolescent, and Pediatric Patients in Studies 332, 311, and 232

Authors: Dr. Christian Brandt, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #020

Wednesday April 21

10:30 AM – 11:00 AM

Perampanel Monotherapy for the Treatment of Epilepsy: Evidence From a Clinical Trial and Real-World Use

Authors: Dr. Antonio Gil-Nagel, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #007

Efficacy and Safety of Low-and High-Dose Perampanel as First Adjunctive Therapy in Patients with Partial-Onset Seizures (POS): Post Hoc Analysis of the FAME Study

Authors: Dr. Dae Won Seo, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #018

ELEVATE Study 410 Initial Results: Phase IV Study of Perampanel as Monotherapy or First Adjunctive Therapy in Patients Aged ≥ 4 Years with Partial-onset or Primary Generalized Tonic-Clonic Seizures

Authors: Dr. Vineet Punia, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #109

Health State Utility Values in Paediatric Subjects with Partial Onset Seizures (POS) or Primary Generalized Tonic Clonic Seizures (PGTCS) Receiving Adjunctive Perampanel

Authors: Dr. Andrew Trigg, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #117

Sunday, April 17

12:00 PM – 12:30 PM

Perampanel as Early Add-on Therapy for Epilepsy Patients with Focal and Generalized Seizures Treated in Clinical Practice

Authors: Dr. Estevo Santamarina, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #111

Tuesday, April 20

3:00 PM – 7:00 PM

Perampanel Monotherapy in Epilepsy Patients with Focal and Generalized Seizures: Real-World Experience

Authors: Dr. Taoufik Alsaadi, et al

Perampanel

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #021

Wednesday April 21

6:00 PM – 7:00 PM

Effectiveness and Tolerability of Perampanel in Epilepsy Patients Treated in Routine Clinical Practice: A Global Pooled Analysis Study

Authors: Dr. Wendyl D'Souza, et al

Lorcaserin

Epilepsy/Clinical Neurophysiology (EEG)

Poster presentation

Abstract #017

Tuesday, April 20

2:00 PM – 2:30 PM

MOMENTUM (Study 304): A Multicenter, Phase III, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of Adjunctive Lorcaserin (LOR) in Patients with Dravet Syndrome (DS)

Authors: Dr. Orrin Devinsky, et al

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 Lecanemab (BAN2401)
Lecanemab is an investigational humanized monoclonal antibody for Alzheimer's disease that is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab selectively binds to neutralize and eliminate soluble, toxic Aβ aggregates (protofibril) 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. 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 October 2017.

Currently, lecanemab 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.

2.  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.

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 lecanemab, anti-amyloid beta (Aβ) protofibril antibodies, and the companies plan to pursue marketing authorizations for aducanumab and lecanemab worldwide. If approved, the companies will also co-promote aducanumab and lecanemab 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 lecanemab 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 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.

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 wakefulnessiv 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.v

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 FYCOMPA (perampanel)

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.vi

FYCOMPA, an oral medication, is a 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 in the event of a missed dose, fluctuations in plasma levels of FYCOMPA are relatively stable due to its long half-life.

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).

IMPORTANT SAFETY INFORMATION FOR FYCOMPA

WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS


- Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA

- These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression

- Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking FYCOMPA or after discontinuing FYCOMPA

- Closely monitor patients particularly during the titration period and at higher doses

- FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening

SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
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.

SUICIDAL BEHAVIOR AND IDEATION
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.

DIZZINESS AND GAIT DISTURBANCE
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.

SOMNOLENCE AND FATIGUE
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
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.

DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)
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.

WITHDRAWAL OF AEDs
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.

MOST COMMON ADVERSE REACTIONS
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.

DRUG INTERACTIONS
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.

PREGNANCY AND LACTATION
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.

HEPATIC AND RENAL IMPAIRMENT
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.

DRUG ABUSE AND DEPENDENCE
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.v

Please see full Prescribing Information, including Boxed WARNING.

7.  About Lorcaserin
Lorcaserin is a selective serotonin 5-HT2c receptor agonist. Stimulation of 5-HT2c receptors with lorcaserin may increase GABA-mediated inhibition and result in reduced seizure activity in Dravet Syndrome patients.ii, vii In September 2020, Eisai announced that it initiated a Phase 3 clinical study, MOMENTUM 1 (Study 304) of lorcaserin in patients with Dravet Syndrome, a severe type of epilepsy characterized by prolonged seizures that begin in the first year of life. It is a rare condition that affects one in 20,000 to 40,000 people worldwide.viii In addition to the MOMENTUM 1 Study, Eisai is continuing the lorcaserin expanded access program (EAP) (Study 405, NCT 04457687), also known as the MOMENTUM 2 Study.ix

8.  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.

Swanson C et al. Treatment of early AD subjects with BAN2401, an anti- Aβ protofibril monoclonal antibody, significantly clears amyloid plaque and reduces clinical decline. Alzheimers Dement. 2018;14(7):1668. 10.1016/j.jalz.2018.07.009.
ii Data on File.  
iii Epilepsy Foundation. Dravet Syndrome. Available at https://www.epilepsy.com/learn/types-epilepsy-syndromes/dravet-syndrome. Accessed March 2021.
iv Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2011;51:243–266.
v Eisai Inc. DAYVIGO Full Prescribing Information. 2021.
vi Eisai Inc. FYCOMPA Full Prescribing Information. 2021.
vii Griffin A et al. Clemizole and modulators of serotonin signaling suppress seizures in Dravet syndrome. Brain. 2017:140;669–683. 10.1093/brain/aww342.
viii Clinicaltrials.gov. A Study of Lorcaserin as Adjunctive Treatment in Participants With Dravet Syndrome (MOMENTUM 1) https://www.clinicaltrials.gov/ct2/show/NCT04572243?term=MOMENTUM+1&draw=2&rank=1. Accessed April 2021.
ix Clinicaltrials.gov. Extended Access Program With Lorcaserin For The Treatment of Dravet Syndrome and Other Refractory Epilepsies. https://clinicaltrials.gov/ct2/show/NCT04457687?term=NCT04457687&draw=2&rank=1. Accessed April 2021.

Contact:

Eisai Inc.
Chris Vancheri
551-305-0050
christopher_vancheri@eisai.com                                               

 

SOURCE Eisai Inc.

Type Press Release

Date Released April 16, 2021

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