Phase III Study Shows Eisai's First-In-Class Treatment Fycompa® (Perampanel) Significantly Reduces Primary Generalised Tonic-Clonic (PGTC) Seizures

Hatfield, England (ots/PRNewswire) -

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/U.S JOURNALISTS

Primary endpoint met for Fycompa(R)(perampanel) as adjunctive
therapy for

refractory generalised tonic-clonic seizures

Phase III data announced today demonstrate control of primary
generalised tonic-clonic seizures (PGTC) with adjunctive Fycompa(R)
(perampanel), Eisai's first-in-class epilepsy.[1] 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.[2]

Study 332 is 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 anti-epileptic drugs (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 (greater than or equal to50% 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.[1]

The most frequently observed adverse events (10% in the perampanel
arm and greater than placebo) were dizziness, fatigue and headache,
irritability and somnolence. The adverse event profile observed in
this study was similar to that observed in other Fycompa studies.[1]

"Tonic-clonic seizures can have serious consequences for patients
and new effective treatment options are always needed. We are pleased
that study 332 has reported positive outcomes," commented Dr Makarand
Bagul, Director, Neurology EMEA Eisai Medical Strategy Lead .

Based on these results, Eisai plans to submit an application to
the European Commission in 2014 for an indication expansion for
perampanel to include the adjunctive treatment of PGTC seizures in
people with epilepsy.

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.[3] 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[2] 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. Fycompa is now approved in more than 35 countries
worldwide.

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(R) (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.[2]

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.[2]

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

About Study 332[1]

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.[4] 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).[5] 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.[5]

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(R) (perampanel) for the adjunctive treatment for partial onset
seizures, with or without secondarily generalised seizures, in patients with epilepsy
aged 12 years and older
- Zonegran(R) (zonisamide) as monotherapy in the treatment of partial seizures,
with or without secondary generalisation, in adults with newly diagnosed epilepsy and
as adjunctive therapy in the treatment of partial seizures, with or without secondary
generalisation, in adults, adolescents, and children aged 6 years and above (Zonegran
is under license from the originator Dainippon Sumitomo Pharma)
- Zebinix(R) (eslicarbazepine acetate) as adjunctive therapy in adults with
partial onset seizures, with or without secondary generalisation (Zebinix is under
license from BIAL)
- Inovelon(R) (rufinamide) for the adjunctive therapy in the treatment of
seizures associated with Lennox-Gastaut syndrome (LGS) in patients four years of age
and older (Rufinamide was originally developed by Novartis)

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 the United Kingdom, Austria,
Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland,
Italy, Norway, Portugal, Russia, Slovakia, Spain, Switzerland,
Sweden, the Netherlands and the Middle East.

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

References

1. Data on file, Eisai Co. Ltd

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

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

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

5. Epilepsy Action. Generalised
seizures.https://www.epilepsy.org.uk/info/seizures/generalised
(accessed June 2014)

6. Epilepsy in the WHO European Region: Fostering Epilepsy Care in
Europe.http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.p
df [http://www.ibe-epilepsy.org/downloads/EURO Report 160510.pdf ]
[http://www.ibe-epilepsy.org/downloads/EURO Report 160510.pdf ]
(accessed June 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: June 2014

Job code: Perampanel-UK2165

ots Originaltext: Eisai Europe Limited
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Media Enquiries Eisai Europe Ltd Cressida Robson/Ben Speller
+44(0)7908-314-155/+44(0)845-676-1607 Cressida_Robson@eisai.net
Ben_Speller@eisai.net Tonic Life Communications Frances Murphy/Nicola
Lilley +44(0)207-798-9262 /+44(0)207-798-9905
frances.murphy@toniclc.com
nicola.lilley@toniclc.com