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°®¶¹´«Ã½. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its in-house-discovered antiepileptic drug (AED) Fycompa® (perampanel hydrate) has been approved in Japan as an adjunctive therapy for partial-onset seizures (including secondarily generalized seizures) or primary generalized tonic-clonic seizures in patients with epilepsy showing inadequate response to other AEDs.

The approval was based on the results of a Phase Ⅲ clinical study (Study 335)¹ of Fycompa administered as an adjunctive therapy in patients aged 12 years and older with refractory partial-onset seizures conducted in Japan and Asia, as well as the results of a global Phase Ⅲ clinical study (Study 332)² of Fycompa administered as an adjunctive therapy in patients aged 12 years and older with primary generalized tonic-clonic (PGTC) seizures.
In Study 335, Fycompa demonstrated a statistically significant reduction in the primary endpoint of seizure frequency at doses of 8 mg/day and 12 mg/day, compared to placebo. In Study 332, Fycompa demonstrated a statistically significant reduction in the primary endpoint of PGTC seizure frequency compared to placebo, and 30.9% of patients treated with Fycompa were free of PGTC seizures during the 13 week maintenance period (12.3% for placebo). The most common adverse events (≥10% in the perampanel arms and greater than placebo) observed in Studies 332 and 335 were dizziness, fatigue, headache, somnolence and irritability.

Discovered at Eisai's Tsukuba Research Laboratories and developed in-house, Fycompa is a first-in-class AED, available in tablet form as a once-daily oral dose. It is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic AMPA receptors. Fycompa is currently approved in more than 45 countries and territories, including Europe and the United States, as an adjunctive treatment of partial-onset seizures (with or without secondarily generalized seizures) in adult and adolescent patients with epilepsy 12 years of age and older. Fycompa has been also been approved in more than 35 countries, including Europe and the United States, for the adjunctive therapy of PGTC seizures in patients with epilepsy 12 years of age and older.

Epilepsy affects approximately 1 million people in Japan. As approximately 30% of patients with epilepsy are unable to control their seizures with currently available AEDs,³ this is a disease with significant unmet medical needs. Generalized tonic-clonic seizures are one of the most severe forms of epileptic seizures as they can cause significant injury to patients from falling down suddenly, and the frequency of these seizures is the most important risk factor associated with sudden unexpected death in epilepsy (SUDEP).⁴

Eisai considers neurology a therapeutic area of focus, and by providing Fycompa as a new treatment option in Japan in addition to the AEDs Inovelon® and Fostoin® as part of an extensive epilepsy product portfolio, Eisai seeks to make continued contributions to address the diverse needs of, as well as increasing the benefits provided to, patients with epilepsy and their families.

Fycompa is a first-in-class AED discovered and developed by Eisai. With epileptic seizures being mediated by the neurotransmitter glutamate, the agent is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic AMPA receptors. Fycompa is available in tablet form as a once-daily oral dose.
The agent is currently approved in more than 45 countries and territories, including Europe and the United States, as an adjunctive treatment of partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 12 years of age and older.
In addition, Fycompa has been approved in more than 35 countries, including Europe and the United States for the adjunctive therapy of primary generalized tonic-clonic (PGTC) seizures in patients with epilepsy 12 years of age and older. More specifically, Eisai has obtained approval for the agent indicated in the United States as an adjunctive treatment of PGTC seizures in patients with epilepsy 12 years of age and older, and in Europe as an adjunctive treatment of PGTC seizures in adult and adolescent patients from 12 years of age with idiopathic generalized epilepsy.
In Japan, a new drug application was submitted in July 2015, and Eisai has now obtained approval of Fycompa indicated as an adjunctive therapy for partial-onset seizures (including secondarily generalized seizures) or primary generalized tonic-clonic seizures in patients with epilepsy showing inadequate response to other AEDs Meanwhile, Eisai submitted applications for the approval of an additional oral suspension formulation of perampanel in Europe and the United States in June 2015, and is conducting Phase Ⅱ studies in Europe and the United States for partial-onset epilepsy in pediatric patients.

Neurons transmit information via synapses. When an electric signal is transmitted to a neuron, neurotransmitters are secreted to the synaptic cleft from vesicles on synapses. When neurotransmitters bind with receptors located on the cellular membrane of the next neuron, an electrical signal is generated and information is transmitted.
Glutamate is an excitatory neurotransmitter widely used throughout the central nervous system. There are various types of glutamate receptors including AMPA receptors, NMDA receptors and kainate receptors. Expressed in most central nerve cells, AMPA receptors mediate extremely fast synaptic transmission, and are thought to play a central role in the incidence and transmission of epileptic seizures.

Epilepsy affects approximately 1 million people in Japan, 2.9 million people in the United States, 6 million people in Europe, and approximately 60 million people worldwide. As approximately 30% of patients with epilepsy are unable to control their seizures with currently available AEDs,³ this is a disease with significant unmet medical needs.
Epilepsy is broadly categorized by seizure type, with partial-onset seizures accounting for approximately 60% of epilepsy cases and generalized seizures accounting for approximately 40%. In a partial-onset seizure, an abnormal electrical disturbance occurs in a limited area of the brain, and sometimes may subsequently spread throughout the brain, becoming a generalized seizure (known as a secondarily generalized seizure). In a generalized seizure, abnormal electrical disturbances occur throughout the brain, and can be followed by a loss of consciousness or physical symptoms manifested throughout the whole body.
PGTC seizures are one of the most common and most severe forms of generalized seizures, accounting for approximately 60% of generalized epilepsy and approximately 20% of all epilepsy cases.⁵
Generalized tonic-clonic seizures are one of the most severe forms of epileptic seizures as they can cause significant injury to patients from falling down suddenly, and the frequency of these seizures is the most important risk factor associated with sudden unexpected death in epilepsy (SUDEP).⁴
For the majority of patients, a generalized tonic-clonic seizure begins with a loss of consciousness without any prior warning symptoms and a sudden contraction of the tonic muscles, causing the patient to fall down (tonic phase). This is followed by violent convulsions (clonic phase) until the muscles finally relax, and the patient is left with a disturbance of consciousness. As this is a serious event, it is seen as a major hindrance on daily life. While the seizure generally only lasts a few minutes, the patient will often feel confused, groggy or drowsy for a short period of time before returning to normal.