Eisai Presents Data on Perampanel and First and Largest U.S. Study on Caregiver Burden in Epilepsy at the 69th Annual American Epilepsy Society Meeting

News provided by

Dec 02, 2015, 08:00 ET

Eisai logo

WOODCLIFF LAKE, N.J., Dec. 2, 2015 /PRNewswire/ -- Eisai Inc. announced today that 21 posters highlighting perampanel data and an interim analysis from the first and largest caregiver burden study in epilepsy will be presented at the 69^th Annual American Epilepsy Society Meeting, taking place December 4-8, 2015, in Philadelphia, PA.

"We are pleased to present these data to the scientific community," said Lynn Kramer, MD, President of the Neuroscience and General Medicine Product Creation Unit and Chief Clinical Officer of Eisai Product Creation Systems, Eisai's research and development organization. "Eisai is committed to advancing epilepsy care and making contributions to help address the diversified needs of epilepsy patients and their families as part of its human health care (hhc) mission."

The following perampanel data will be presented during poster sessions on Saturday, December 5^th through Monday, December 7^th. Highlights include the following:

Poster Title	Poster Number
Saturday, December 5^th, 2015, 12:00-2:00pm
Long-Term Perampanel Treatment in Patients with Drug-Resistant Partial Seizures: > 75% Responders and Seizure-Free Status This sub-analysis reports on subjects with drug-resistant partial seizures who have experienced a 75% reduction in seizures or seizure freedom with long-term perampanel therapy.	1.196
Effect of Adjunctive Perampanel in Pediatric Subjects with Epilepsy: Preliminary Safety and Efficacy Results from Study 232 This analysis reports preliminary safety and efficacy findings from an open-label Phase II pilot study of perampanel oral suspension in pediatric subjects aged 2 to <12 years old with epilepsy.	1.184
Pharmacokinetics of Perampanel in Children with Epilepsy Aged 2-<12 Years This analysis reports the pharmacokinetics of perampanel as adjunctive therapy in children compared to adolescents.	1.187
Efficacy of Perampanel by Baseline Seizure Frequency in Patients with Partial Seizures (Phase III Double-Blind Studies) This post-hoc analysis evaluates the efficacy of perampanel in subjects with drug-resistant partial seizures based on their seizure frequency at the time of enrollment in three Phase III perampanel double-blind studies.	1.188
Suicidality Events in Patients with Primary Generalized Tonic-Clonic Seizures (PGTCS): A Review of Study 332 This analysis of a randomized double-blind, placebo-controlled study of subjects 12 years of age or older with uncontrolled PGTCS reviews suicidal behavior and ideation using adverse event reporting and the Columbia Suicide Severity Rating Scale (C-SSRS).	1.189
Psychiatric and Behavioral Events with Perampanel in Patients with Primary Generalized Tonic-Clonic Seizures (PGTCS): Study 332 This analysis of a randomized double-blind, placebo-controlled study of subjects 12 years of age or older with uncontrolled PGTCS reviews psychiatric and behavioral events using adverse event reporting to further understand perampanel and psychiatric and behavioral events.	1.190
Subanalysis by Baseline Antiepileptic Drugs (AEDs): Results from Perampanel Study 332 in Patients with Primary Generalized Tonic-Clonic Seizures (PGTCS) This sub-analysis evaluates the efficacy and safety of perampanel by baseline antiepileptic drugs in subjects 12 years of age or older with uncontrolled PGTCS and taking 1-3 concomitant antiepileptic drugs.	1.191
Review of Pregnancy Events in Perampanel Clinical Studies This review compiles pregnancy data from perampanel clinical studies.	1.192
Effect of Duration of Epilepsy on Adjunctive Perampanel Treatment in Patients with Drug-Resistant Partial Seizures This post-hoc analysis reports efficacy results of perampanel adjunctive therapy in subjects with drug-resistant partial seizures stratified by duration of epilepsy.	1.193
Analysis of Falls in the Phase III Perampanel Study of Primary Generalized Tonic-Clonic Seizures (PGTCS) This analysis is a systematic review of reported falls evaluated to establish whether the fall was related to a seizure.	1.194
Clinical Laboratory Evaluation and Treatment-Emergent Adverse Events Related to Cardiac, Hepatic and Renal Disorders; Perampanel PGTC Phase III Study This analysis evaluated laboratory tests and treatment-emergent adverse events related to these tests, as well as cardiac-, hepatic- and renal-related treatment-emergent adverse events, in subjects aged 12 years or older enrolled in a primary generalized tonic-clonic seizure Phase III study.	1.195
Model-Predicted Relationships Between Perampanel Plasma Concentrations and Efficacy for Partial-Onset Seizures (POS) and Primary Generalized Tonic-Clonic (PGTC) Seizures This analysis of four randomized double-blind, placebo-controlled study of subjects aged > 12 years with idiopathic generalized epilepsy and uncontrolled PGTCS presents equivalent pharmacokinetic/pharmacodynamics (PK/PD) data from patients with partial onset seizures and primary generalized tonic-clonic seizures.	1.211
Protein Binding of Perampanel in Human Plasma: Does Protein-Binding Displacement Occur? These in vitro analyses evaluated the potential for perampanel to act as a displacer and the displacement of perampanel by other commonly used anti-epileptic drugs (phenytoin or valproate) or a highly bound reference drug (warfarin).	1.212
Pharmacokinetics of Adjunctive Perampanel in Patients with Partial-Onset Seizures and Primary Generalized Tonic-Clonic (PGTC) Seizures in Idiopathic Generalized Epilepsy (IGE): Pooled Data from Four Randomized, Double-Blind Phase III Studies This univariate analysis investigated the effect of weight, age, sex, race, liver and renal function markers, dose, seizure type, and presence of concomitant enzyme-inducing antiepileptic drugs (EIAEDs) on the apparent clearance (CL/F) of perampanel.	1.214
Budget Impact of Perampanel for Treating Primary Generalized Tonic Clonic Seizures (PGTC) Patients in Addition to Existing Partial-Onset Seizures (POS) Patients in the US This study estimated the incremental Budget Impact (BI) of utilizing perampanel to treat primary generalized tonic clonic seizures (PGTC) patients in addition to existing partial-onset seizures (POS) in patients who are 12 years of age and older in the US using a budget impact model.	1.335
Sunday, December 6, 2015, 12:00 - 2:00pm
Effect of Perampanel on Neuroprotection in the Lithium-Pilocarpine Rat Model of Status Epilepticus This study examines the effect of perampanel on neuroprotection one week after the occurrence of status epilepticus.	2.239
Efficacy and Tolerability of Perampanel in Patients with Secondarily Generalized (SG) or Primary Generalized Tonic-Clonic Seizures (PGTC): a Pooled Analysis of Four Randomized Phase III Studies This post-hoc analysis evaluated efficacy and tolerability of perampanel across all four Phase III studies in patients with secondarily generalized or primary generalized tonic-clonic seizures.	2.250
Efficacy and Safety of Adjunctive Perampanel (PER) in Adolescents with Inadequately Controlled Partial-Onset Seizures (POS): Randomized, Double-Blind and Open-Label Extension (OLE) Study This is an analysis of long-term efficacy and tolerability of adjunctive perampanel from the blinded and open-label extension phases of Study 235, a randomized, double-blind, placebo-controlled Phase II study of adjunctive perampanel in adolescent patients with inadequately controlled partial-onset seizures.	2.263
Monday, December 7, 2015, 12:00 - 2:00pm
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Perampanel as Adjunctive Therapy in Patients with Refractory Partial-Onset Seizures from the Asia-Pacific Region This study investigated the efficacy and safety of perampanel in a Phase III study in patients from the Asia-Pacific region who were male and female, 12 years of age or older, with partial-onset seizures and with or without secondarily generalized seizures.	3.256
Long-Term Cognitive Effects of Adjunctive Perampanel (PER) in Adolescents for Treatment of Partial-Onset Seizures (POS): Randomized, Double-Blind and Open-Label Extension (OLE) Study This analysis is an examination of the long-term cognitive effects of adjunctive perampanel, based on the blinded and open-label extension phases of Study 235.	3.260
Effect of Adjunctive Perampanel on Growth and Development in Adolescents with Inadequately Controlled Partial-Onset Seizures (POS): Randomized, Double-Blind and Open-Label Extension (OLE) Study This is an analysis of the long-term effects of perampanel on growth and development of adolescent patients from the blinded and open-label extension phases of Study 235.	3.262

Eisai is also presenting the following poster on caregiver burden associated with epilepsy care:

Poster Title

Poster Number

Saturday, December 5^th, 2015, 12:00-2:00pm

Caregiver Burden: An Under-Recognized Aspect of Epilepsy Care

This is an interim analysis of an ongoing cross-sectional survey of 500 caregivers of epilepsy patients to assess overall burden associated with caring for persons with epilepsy.

1.374

About FYCOMPA^® (perampanel)
The above publications do not necessarily contain information that is consistent with the U.S. prescribing information for FYCOMPA (perampanel).

FYCOMPA is indicated as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

FYCOMPA, an FDA approved 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.

FYCOMPA is supplied as 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg film-coated tablets. FYCOMPA has been designated by the U.S. Drug Enforcement Administration as a federally-controlled substance (CIII).

Perampanel, approved in over 40 countries and currently available in 22 countries as FYCOMPA, was discovered and developed by Eisai. Over 35,000 patients globally have been treated with FYCOMPA.

FYCOMPA (perampanel) CIII Indication and Important Safety Information

Indication:
FYCOMPA (perampanel) is indicated as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

	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 clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of clinical trial patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/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. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. 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 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 or 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 seizures clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg/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 seizures clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg/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 primary generalized tonic-clonic 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 seizures trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 7% of placebo patients. Fatigue-related events were reported in 12% and 15% of patients in the partial-onset seizures trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 5% of placebo patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the primary generalized tonic-clonic 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.

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

Withdrawal of AEDs
A gradual withdrawal is generally recommended with antiepileptic drugs 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 (≥5% and ≥1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety.

Drug Interactions
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of FYCOMPA were decreased when administered with carbamazepine, phenytoin, or oxcarbazepine. Concomitant use with strong CYP3A inducers such as St. John's wort or rifampin should be avoided. Multiple dosing of FYCOMPA 12 mg/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.

Pregnancy Category C and Lactation
FYCOMPA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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 a nursing woman.

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 drug substance and has the potential to be abused or lead to drug dependence.

Please see Full Prescribing Information

Eisai Inc.
At Eisai Inc., human health care 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 help address unmet medical needs. We are a fully integrated pharmaceutical business with discovery, clinical, manufacturing and marketing capabilities. Our key areas of commercial focus include oncology and specialty care (Alzheimer's disease, epilepsy and metabolic disorders). To learn more about Eisai Inc., please visit us at www.eisai.com/US.

Eisai Inc. has affiliates that are part of a global product creation organization that includes R&D facilities in Massachusetts, New Jersey and Pennsylvania, as well as a global demand chain organization that includes facilities in Maryland and North Carolina. Eisai's global areas of R&D focus include neuroscience; oncology; metabolic disorders; vascular, inflammatory and immunological reaction; and antibody-based programs.