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ºÚÁÏÍø., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “ºÚÁÏÍø”) announced today that it has presented the results from a Phase Ⅲ clinical study (Study 332) of its in-house developed antiepileptic drug (AED) Fycompa® (perampanel) in patients with primary generalized tonic-clonic (PGTC) seizures, one of the most severe forms of generalized seizures. The data was presented at the 68th American Epilepsy Society (AES) Annual Meeting held from December 5 to 9 in Seattle, Washington in the United States (Abstract No.: 2389). Furthermore, this presentation was selected by the AES for its official program, and was highlighted at a press conference on Sunday, December 7.

Study 332 was a double-blind, randomized, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive Fycompa therapy in 164 patients aged 12 years and older with uncontrolled PGTC seizures. In this study, eligible patients receiving one to a maximum of three AEDs were randomized to receive Fycompa or placebo in a 1:1 ratio.

The primary endpoints of the study were change in PGTC seizure frequency (percent change from Baseline in PGTC seizure frequency per 28 days) and responder rate (percentage of patients who experienced a 50% or greater reduction in PGTC seizure frequency).^* A reduction in PGTC seizure frequency of 76.5% was observed in the Fycompa group, which was statistically significant when compared to a reduction of 38.4% for placebo (p<0.0001). Additionally, the responder rate for Fycompa was 64.2%, which was a statistically significant improvement over the responder rate for placebo of 39.5% (p=0.0019).
In addition, in this study which enrolled patients who had been unable to adequately control PGTC seizures with existing AEDs, 30.9% of patients treated with Fycompa were free of PGTC seizures (12.3% for placebo) during the 13 week Maintenance period.

Furthermore, the most common adverse events (>10% in the Fycompa arm and greater than placebo) for Fycompa and placebo were, respectively, dizziness (32.1% vs 6.1%), fatigue (14.8% vs 6.1%), headache (12.3% vs 9.8%), somnolence (11.1% vs 3.7%) and irritability (11.1% vs 2.4%).

Fycompa is a first-in-class AED discovered and developed by ºÚÁÏÍø. With epileptic seizures being primarily 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 approved in more than 40 countries primarily in Europe and North America as an adjunctive treatment for partial-onset seizures (with or without secondary generalized seizures) in patients with epilepsy aged 12 years and older, and has been launched in 15 countries around the world.

Also, applications seeking an additional indication for the adjunctive treatment of PGTC seizures in patients with epilepsy aged 12 years and older based on the results of this study were filed with regulatory authorities in Europe and the United States in August 2014.

ºÚÁÏÍø considers epilepsy a therapeutic area of focus and by providing multiple treatment options in addition to Fycompa as part of an extensive epilepsy product portfolio, ºÚÁÏÍø 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, a novel chemical entity discovered and developed by ºÚÁÏÍø, is a noncompetitive AMPA-type glutamate receptor antagonist. Fycompa is an antiepileptic drug that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic AMPA receptors. The agent is currently approved in more than 40 countries and territories, including Europe and the United States, as an adjunctive treatment (once-daily oral dose) of partial-onset seizures and is also being evaluated in a Phase Ⅲ study (Study 335) in Asia, including Japan.
A Phase Ⅲ study (Study 332) of the agent as an adjunctive therapy for the treatment of primary generalized tonic-clonic (PGTC) seizures conducted in the United States, Europe and Asia, including Japan, met its primary endpoint, and regulatory applications for an indication expansion of the agent are under review in the United States and Europe. The company plans to submit a regulatory application covering both study 332 and study 335 in Japan in fiscal 2015. Furthermore, ºÚÁÏÍø is conducting Phase Ⅱ studies in Europe and the United States for partial-onset epilepsy in pediatric patients.

Epilepsy affects nearly 1 million people in Japan, 2.4 million people in Europe (G5), 2.2 million people in the United States, and more than 50 million people worldwide. 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%. Primary generalized tonic-clonic (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.¹ For the majority of patients, a PGTC 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.