Eisai Submits EU Marketing Authorisation Application for Fycompa® (perampanel) as Adjunctive Therapy in People With Uncontrolled Primary Generalised Tonic-Clonic (PGTC) Seizures

HATFIELD, England, August 20, 2014 /PRNewswire/ --

Eisai has submitted a Marketing Authorisation Application to the European Commission for its first-in-class anti-epileptic drug (AED) Fycompa^® (perampanel) as an adjunctive treatment of primary generalised tonic-clonic seizures (PGTC). Perampanel is currently indicated for the adjunctive treatment of partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older.^[1]

Generalised tonic-clonic seizures are one of the most dangerous types of seizure.^[2] The seizures start with a loss of consciousness and a sudden contraction of the muscles, which can cause the person to fall down (tonic phase). This is followed by violent convulsions (clonic phase) until the muscles finally relax.^[3]

The filing in this new indication is based on data from Study 332,^[4] a double-blind, randomised, placebo-controlled, multicentre, parallel-group trial to evaluate the efficacy and safety of adjunctive perampanel for refractory PGTC seizures. 164 people (>12 years old) with PGTC seizures, despite treatment with one to three concomitant AEDs were randomised to receive perampanel or placebo in a 1:1 ratio. Results demonstrate that perampanel significantly reduces PGTC seizure frequency and improved responder rates (≥50% reduction in seizure frequency per 28 days in the maintenance period, relative to baseline), the study's two primary outcome measures, when compared to placebo.

The most frequent adverse events (10% in the perampanel arm and greater than placebo) are dizziness, fatigue and headache, irritability and somnolence. The adverse event profile is similar to that for other perampanel studies.^[4]

"Tonic-clonic seizures are very serious and can have a profound effect on quality of life for people with epilepsy. We believe that perampanel has great potential in this area and have filed in Europe for a license extension to include the adjunctive treatment of PGTC seizures in people with epilepsy," commented Neil West, Vice President EMEA, Global Neurology Business Unit at Eisai.

Perampanel is the only licensed AED to selectively target AMPA receptors, a protein in the brain which plays a critical role in the spread of seizures.^[5] This mechanism of action is different to all other, currently available AEDs. In addition, perampanel has the added benefit of convenient, once-daily dosing at bedtime^[1] and, significantly, is the only new-generation partial epilepsy treatment approved to treat adolescents (>12 years) with epilepsy from launch.

Discovered and developed by Eisai in Europe and Japan, perampanel is manufactured in the UK and was approved by the European Commission on 23 July 2012. Perampanel has been approved in more than 35 countries.

The on-going clinical investigation of perampanel for different seizure types underscores Eisai's human health care (hhc) mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and wellbeing of people worldwide.

Notes to Editors  

About Fycompa^® (perampanel)  

Perampanel is indicated for the adjunctive treatment of partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older.^[1]

Perampanel is a highly selective, non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptor antagonist that has demonstrated seizure reduction in Phase II and III studies. AMPA receptors, widely present in almost all excitatory neurons, transmit signals stimulated by the excitatory neurotransmitter glutamate within the brain and are believed to play a role in central nervous system diseases characterised by excess neuroexcitatory signalling including epilepsy.^[1]

Further information for healthcare professionals can be found at http://www.fycompa.eu  

About Study 332^[4]

Study population:        164 patients aged 12 years and older with PGTC seizures receiving one to maximum of three anti-epileptic drugs

Primary objective:       To demonstrate the efficacy of adjunctive perampanel therapy compared to placebo on PGTC seizures

Treatment administered: (Placebo controlled) Perampanel oral tablets, once daily, up to 8 mg/day (titration phase), randomised dose 8 mg/day
                        (maintenance phase)

Duration of treatment:   Pre-randomisation phase (screening and baseline periods): up to 12 weeks

Randomisation phase (treatment): 17 weeks (titration phase, 4 weeks; maintenance phase, 13 weeks)

Extension phase:         Over 38 weeks

Study locations:         U.S., Europe, Japan, Asia

Primary endpoint:        Percent change in PGTC seizure frequency (US):

                             - Percent change from baseline in PGTC seizure frequency per 28 days during treatment

                               Responder rate (EU):

                             - Percentage of patients who experience a 50% or greater reduction in PGTC seizure frequency per 28 days in the maintenance
                               period relative to baseline

About Primary Generalised Tonic-Clonic Seizures  

Generalised tonic-clonic seizures are one of the most dangerous types of seizure.^[2] For the majority of patients, a primary generalised tonic-clonic (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).^[2] 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 or drowsy for a short period of time before returning to normal.^[3]

About Epilepsy   

Epilepsy is one of the most common neurological conditions in the world, affecting approximately eight in 1,000 people in Europe, and an estimated 50 million people worldwide.^[6],[7] Epilepsy is a chronic disorder of the brain that affects people of all ages. It is characterised by abnormal discharges of neuronal activity which causes seizures. Seizures can vary in severity, from brief lapses of attention or jerking of muscles, to severe and prolonged convulsions. Depending on the seizure type, seizures may be limited to one part of the body, or may involve the whole body. Seizures can also vary in frequency from less than one per year, to several per day. Epilepsy has many possible causes but often the cause is unknown.

About Eisai EMEA in Epilepsy   

Eisai is committed to developing and delivering highly beneficial new treatments to help improve the lives of people with epilepsy. The development of AEDs is a major strategic area for Eisai in Europe, the Middle East, Africa, Russia and Oceania (EMEA).

In the EMEA region, Eisai currently has four marketed treatments including:

• Fycompa® (perampanel) for use as an adjunctive treatment for partial onset seizures, with or without secondarily generalised seizures, in patients with epilepsy aged 12 years and older
• Inovelon® (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients ≥4 years. (Rufinamide was originally developed by Novartis)
• Zebinix® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial onset seizures, with or without secondary generalisation. (Zebinix is under license from BIAL)
• Zonegran® (zonisamide) as monotherapy in adults and adjunctive therapy in adults, adolescents and children aged six years and above with partial onset seizures, with or without secondary generalisation. (Zonegran is under license from the originator Dainippon Sumitomo Pharma)

About Eisai   

Eisai is one of the world's leading research and development (R&D) based pharmaceutical companies and we define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call human health care (hhc).

Eisai concentrates its R&D activities in three key areas:

• Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight management
• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc.
• Vascular/Immunological reaction including: thrombocytopenia, rheumatoid arthritis, psoriasis, inflammatory bowel disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 10,000 people worldwide. From its EMEA Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to include Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Iceland, Ireland, Italy, the Middle East, the Netherlands, Norway, Portugal, Russia, Slovakia, Spain, Switzerland, Sweden, and the United Kingdom.

For further information please visit our web site: http://www.eisai.co.uk

References  

1. Fycompa, Summary of Product Characteristics (updated November 2013): http://www.medicines.org.uk/emc/medicine/26951/

2. Blumenfeld H et al. Cortical and subcortical networks in human secondarily generalized tonic-clonic seizures. Brain. 2009:132:999-1012

3. Epilepsy Action. Generalised seizures. https://www.epilepsy.org.uk/info/seizures/generalised-seizures (accessed July 2014)

4. Data on file, Eisai Co. Ltd.

5. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents 2011:11:56-63

6. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf (Accessed July 2014)

7. Pugliatti M et al. Estimating the cost of epilepsy in Europe: A review with economic modeling. Epilepsia 2007:48(12):2224-2233.

Date of preparation: August 2014

Job code: perampanel-UK2172