New Fycompa® (perampanel) Data on Long-term Seizure Control in Different Seizure Types Presented at the 12th European Congress on Epileptology (ECE) 2016

Hatfield, England (ots/PRNewswire) -

FOR EMEA MEDIA ONLY - NOT FOR SWISS/AUSTRIAN/CZECH REPUBLIC
JOURNALISTS

New data presented from registry study for Inovelon® (rufinamide)
for people with Lennox-Gastaut Syndrome

New data presented today at the 12th European Congress on
Epileptology (ECE) of an open-label extension study of the pivotal
Phase III randomised, double-blind, placebo-controlled, clinical
Study 332, showed that long-term adjunctive perampanel for up to two
and a half years (142 weeks) provided sustained seizure control and
was generally well tolerated in poorly controlled patients with
primary generalised tonic clonic (PGTC) seizures, in idiopathic
generalised epilepsy (IGE).[1]

Perampanel is indicated in the European Union for adjunctive
treatment of partial-onset seizures, with or without secondarily
generalised seizures, and for adjunctive treatment of PGTC seizures
in patients with IGE aged 12 years and older.[2]

In the open-label extension study, 138 patients received
once-daily adjunctive perampanel for up to 136 weeks following
dose-optimisation in a 6-week blinded conversion period. Sixty
patients discontinued perampanel during the extension study, most
(n=41) due to reasons other than adverse events or inadequate
therapeutic response. By the end of the conversion period, results
were as follows:[1]

Seizure Measure N=138

Perampanel (n=68) Placebo (n=70)
Median per cent
change
in PGTC seizure
frequency -93.1%
-100%
50% responder rates 75.0%
74.3%

Treatment-emergent adverse events were seen in 120 patients
(87.0%) with 20 patients (14.5%) having severe adverse events, 18
(13.0%) with serious adverse events, and 13 (9.4%) with adverse
events leading to withdrawal.[1]

"The extension study shows that patients with primary generalised
tonic clonic seizures in idiopathic generalised epilepsy achieve
similar clinical benefits, with consistent tolerability, to those
seen previously in Study 332," comments Eugen Trinka, Professor and
Chair of the Department of Neurology, Paracelsus Medical University,
Salzburg, Austria.

Exploratory outcomes from a post-hoc analysis of the 17-week core
phase of Study 332 showed that compared with placebo, adjunctive
perampanel showed no clear evidence for worsening of myoclonic or
absence seizures.[3] There was a difference in baseline seizure
frequency for myoclonic and absence seizures between perampanel and
placebo groups and the study was not powered to detect differences in
these seizure types.

(n=162)

Seizure Type Perampanel (n=81) Placebo (n=81)

Baseline
myoclonic 29.0%
Baseline absence
37.0%
Perampanel
Placebo
Absence seizure freedom 22.2%
12.1%
Absence seizure worsening 29.6% 45.5%
Myoclonic seizure freedom 16.7% 13.0%

Myoclonic seizure worsening 29.2% 30.4%

The most common adverse events with perampanel in the 17-week core
phase of Study 332 were dizziness, fatigue, headache, somnolence and
irritability.[4]

Data from open-label extension Study 307 in patients with focal
epilepsy treated with adjunctive perampanel for up to four years were
also presented, including seizure outcomes:[5]

Change during last year of 3 Years Perampanel 4 Years
Perampanel
perampanel treatment Exposure (n=436)
Exposure (n=78)
Median % seizure reduction 61.98%
70.63%
Median % seizure reduction
in secondarily
generalised
seizures 87.96%
100%
50% responder rate 59.6% 67.9%

No new safety signals were seen during long-term perampanel

exposure

Final results from a European patient registry study[6] for safety
in 111 patients of all ages (>=4 years) with Lennox-Gastaut Syndrome
(LGS), suggest the potential for rufinamide and 'other' antiepileptic
drugs in the long-term treatment of LGS. At Month 12, the proportion
of patients rated as 'much', or 'very much' improved in control of
all seizures was 12/42 (28.6%) and 5/33 (15.2%) for rufinamide and
other AEDs, respectively.

Treatment-related adverse events were reported for 40.6% for
rufinamide and 27.7% for other AEDs patients, and led to
discontinuation of 7.8% and 2.1% of patients, respectively. The most
frequently reported rufinamide-related adverse events (>=5% patients)
were somnolence (7.8%) and decreased appetite (6.3%). There were no
unexpected safety findings.

Rufinamide is indicated in the European Union as adjunctive
therapy in the treatment of seizures associated with Lennox-Gastaut
Syndrome in patients four years of age and older.[7]

There are limited published data on the treatment of adults with
Lennox-Gastaut Syndrome. In another analysis of this study,[8] data
on adults (>=18 years) were extracted and analysed. Twenty-four
adult patients were included (16 on rufinamide and 8 on another
antiepileptic drug).

At Month 24, the proportion of patients rated as 'much' or 'very
much' improved in control of all seizures was 2/7 (28.6%) and 2/4
(50.0%) for rufinamide and other AEDs, respectively. AED-related
adverse events were reported for 50.0% for rufinamide and 37.5% for
other AEDs patients, and led to discontinuation of 6.3% and 0% of
patients, respectively. The only rufinamide-related adverse event
reported for more than one adult was somnolence (n=2). There were no
unexpected safety findings.

The registry enrolled patients with Lennox-Gastaut Syndrome (age
>=4 years) requiring modification to any anti-epileptic treatment,
including initiation of rufinamide. The primary objective of the
registry was to evaluate long-term safety.[6],[8] Seizure control was
also assessed using a 7-point generic seizure frequency scale (rated
from 'very much worse' to 'very much improved'). A total of 111
patients were enrolled and included in the safety analysis set, of
whom 64 initiated rufinamide and 47 were initially allocated other
antiepileptic drugs. For the analysis of the adult population from
this safety analysis set, 24 patients were included (16 on rufinamide
and 8 on another antiepileptic drug).[8]

"The data presented for perampanel and rufinamide provide new
insights into the long-term care of people with epilepsy. There is no
known cure and people have to live with the consequence of epilepsy
day in and day out. Eisai is committed to understanding the long-term
impact of its treatments, for seizure freedom and safety, and these
results help us to enhance our knowledge of treatment in everyday
life," comments Neil West, Vice President, Global Neurology Business
Group, Eisai EMEA.

The continued development of its epilepsy portfolio 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. Eisai is committed to the
therapeutic area of neurology and to address the unmet medical needs
of people with epilepsy and their families.

Notes to Editors

About Fycompa® (perampanel)

Perampanel is a highly selective, non-competitive AMPA
(alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type
glutamate receptor antagonist. 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.

Since launch, approximately 52,000 people living with epilepsy
across the EMEA region* have been treated with perampanel.[9]

*EMEA countries are Germany, Italy, United Kingdom, Spain, France,
Switzerland, Netherlands, Ireland, Sweden, Norway, Denmark, Austria,
Belgium, Czech Republic, Portugal, Greece, Australia, Russia,
Slovakia, Israel.

Clinical data for Fycompa® (perampanel) - Phase III study 332[4]

Study 332 is a double-blind, randomised, placebo-controlled,
multicentre, parallel-group trial to evaluate the efficacy and safety
of adjunctive perampanel for refractory primary generalised tonic
clonic (PGTC) seizures in idiopathic generalised epilepsy (IGE). 164
people (>=12 years old) with PGTC seizures and IGE (diagnoses
confirmed by independent reviewers), despite treatment with one to
three concomitant AEDs, were randomised to receive perampanel (8 mg/d
or highest tolerated dose) or placebo in a 1:1 ratio.

About Inovelon® (rufinamide)

Rufinamide was approved for adjunctive therapy for Lennox-Gastaut
Syndrome in Europe (under the brand name Inovelon®) in 2007.
Rufinamide is available in 19 European countries as film-coated
tablets containing 100mg, 200mg, and 400mg rufinamide. It is
available in some countries as an oral suspension in orange flavour
40mg/ml concentration. The oral suspension formulation is
bioequivalent to the tablet formulation on a milligram per milligram
basis and is available in Austria, Denmark, France, Finland, Germany,
Netherland, Norway, Portugal, Spain, Switzerland, Sweden and the
United Kingdom.

About Epilepsy

Epilepsy is one of the most common neurological conditions in the
world, affecting approximately 6 million people in Europe, and an
estimated 50 million people worldwide.[10] 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.

For the majority of idiopathic generalised epilepsy patients, a
primary generalised tonic clonic (PGTC) seizure begins with or
without an aura (sensory or psychic phenomena), which is followed by
loss of consciousness and muscle rigidity (tonic phase). This is
followed by violent muscle contractions (clonic phase). 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.[11],[12] PGTC seizures can also result in risk
of injury and sudden unexpected death in epilepsy (SUDEP).[13]

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) is indicated for use as a once-daily,
adjunctive therapy for both primary generalised tonic clonic
seizures in idiopathic generalisation and for partial onset
seizures, with or without secondary generalisation, in patients
with epilepsy aged 12 years or older
- Inovelon® (rufinamide) is indicated for the adjunctive treatment of
seizures associated with Lennox-Gastaut Syndrome in patients >=4
years. (Rufinamide was originally developed by Novartis)
- Zonegran® (zonisamide) is indicated 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 six years
and above. (Zonegran® is under license from the originator
Dainippon Sumitomo Pharma)
- Zebinix® (eslicarbazepine acetate) is indicated as adjunctive
therapy in adult patients with partial onset seizures, with or
without secondary generalisation (Zebinix® is under license from
BIAL)

About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global research and development-based
pharmaceutical company headquartered in Japan. 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 our human health care (hhc) philosophy. With over 10,000
employees working across our global network of R&D facilities,
manufacturing sites and marketing subsidiaries, we strive to realise
our hhc philosophy by delivering innovative products in multiple
therapeutic areas with high-unmet medical needs, including Oncology
and Neurology.

As a global pharmaceutical company, our mission extends to
patients around the world through our investment and participation in
partnership-based initiatives to improve access to medicines in
developing and emerging countries.

For more information about Eisai Co., Ltd., please visit
http://www.eisai.com

References

1. Wechsler R, et al. Long-term safety and efficacy of adjunctive
perampanel in patients with drug-resistant primary generalised tonic
clonic seizures in idiopathic generalised epilepsy: results of an
open-label extension; European Congress on Epileptology 2016:
Abstract #555

2. Fycompa® (perampanel) Summary of Product Characteristics (last
updated March 2016). Available at:
http://www.medicines.org.uk/emc/medicine/26951. Accessed September
2016

3. O'Brien T, et al. Myoclonic and Absence Seizures in Patients
With Idiopathic Generalised Epilepsy (IGE): Exploratory Outcomes in a
Phase III PGTC Study With Adjunctive Perampanel; European Congress on
Epileptology 2016: Abstract #0073

4. French J, et al. Perampanel for tonic clonic seizures in
idiopathic generalised epilepsy. Neurology 2015;85 (11):950-57

5. Perucca E, et al. Marked Reduction in Secondarily Generalised
Seizures in Patients Treated With Perampanel for 3 and 4 Years;
European Congress on Epileptology 2016: Abstract #0074

6. Auvin S, et al. European non-interventional registry study of
antiepileptic drug use in patients with Lennox-Gastaut Syndrome;
European Congress on Epileptology 2016: Abstract #590

7. Inovelon® (rufinamide) SPC - Inovelon Tablets and Oral
Suspension. Available at:
http://www.medicines.org.uk/emc/medicine/20165/SPC/ [updated 6 August
2013]. Accessed September 2016

8. Brandt C, et al. Use of rufinamide and other antiepileptic
drugs in the management of adult patients (>=18 years) with
Lennox-Gastaut Syndrome; European Congress on Epileptology 2016:
Abstract #P622

9. Eisai. Data on File 2016. DOF PER112

10. Epilepsy in the WHO European Region: Fostering Epilepsy Care
in Europe.
http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf.
Accessed September 2016

11. Epilepsy Foundation. Types of Seizures. Available at:
http://www.epilepsy.com/learn/types-seizures. Accessed September 2016

12. Epilepsy Foundation. IGE Summary. Available at: http://www.epi
lepsy.com/information/professionals/about-epilepsy-seizures/idiopathi
c-generalized-epilepsies/idiopathic. Accessed September 2016

13. Smithson WH, et al. Sudden Unexpected Death in Epilepsy:
Addressing the Challenges. Curr Neurol Neurosci Rep 2014; 14(12):502

September 2016

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ots Originaltext: Eisai
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