New First-in-class Epilepsy Treatment Fycompa® (perampanel) Launches in Spain

Hatfield, England (ots/PRNewswire) -

Fycompa(R) (perampanel), the first in an entirely new class of
treatment for partial onset seizures (the most common form of
epilepsy), launches today in Spain. The new therapy 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 the only licensed anti-epileptic drug (AED) to
selectively target AMPA receptors, a protein in the brain which plays
a critical role in the spread of seizures.[2] This mechanism of
action is different to 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 with epilepsy from
launch.

Epilepsy is one of the most common neurological conditions in the
world.[3] Around 400,000 people in Spain live with the condition.[4]

"Almost a third of people with partial epilepsy continue to
experience seizures despite the treatment options currently
available," commented Dr. José Serratosa, an Epileptologist at the
Epilepsy Unit of the Fundación Jiménez Díaz University Hospital,
Madrid. "New treatment options such as this are a welcome addition to
doctors' epilepsy treatment armamentarium."

Perampanel's reimbursement approval in Spain is based on three
randomised, double-blind, placebo-controlled and dose-escalated
global pivotal Phase III studies (304, 305, 306) and an open-label
extension study (307). The three global pivotal studies show
consistent results in the efficacyand tolerability of perampanel as
an adjunctive therapy in people with partial onset seizures, with or
without secondary generalisation.[5],[6],[7 ] The most commonly
reported adverse events were dizziness, somnolence, fatigue,
headache, falls, irritability and ataxia.[5],[6],[7] Results from the
open-label extension study also demonstrate perampanel's efficacy and
favorable tolerability profile over the longer term.[8]

Dr. Javier Sánchez, Medical Manager, Eisai Spain, commented:
"We're pleased to announce the launch of perampanel in Spain. As an
emerging leader in the field of epilepsy, Eisai is committed to
developing innovative therapies to meet the unmet needs of people
with epilepsy who need alternative treatment options to help them
achieve seizure control."

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.

The launch of perampanel in Spain 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 Perampanel

Fycompa 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]

For more information please visit: http://www.fycompa.eu

About the Perampanel Pooled Data (Study 306, 305 and
304)[5],[6],[7]

The pooled Phase III data analysed the efficacy of once-daily
perampanel in reducing partial onset seizures, the most common form
of epilepsy, and its effectiveness and flexibility of use as add-on
therapy. Efficacy end points for studies 304, 305, and 306 were
pooled according to randomised treatment: placebo, perampanel 2, 4, 8
or 12mg. The full ITT (intention-to-treat) analysis set included
1,478 patients from studies 304 (n=387), 306 (n=386) and 306 (n=705).

Median reductions in partial seizure frequency were greater with
perampanel 4 mg (-23.3%), 8 mg (-28.8%), and 12 mg (-27.2%) than
placebo (-12.8%; p<0.01, each dose vs placebo). Median (95% CI)
differences from placebo in changes in partial seizure frequency were
-12.2% (-20.1 to -4.6), -17.9% (-24.1 to -11.8), and -15.8% (-23.0 to
-8.7) for perampanel 4, 8, and 12 mg, respectively.[9]

50% responder rates were greater with perampanel 4 mg (28.5%), 8
mg (35.3%), and 12 mg (35.0%) than placebo (19.3%; p<0.05, each dose
vs placebo). Median reductions in complex partial seizure frequency
were greater with perampanel 4 mg (-31.2%), 8 mg (-35.6%), and 12 mg
(-28.6%) than placebo (-13.9%).[1]

Results from two separate analyses of pooled data from the
perampanel pivotal Phase III clinical trial programme endorse the
efficacy and safety of the new AED at clinically relevant doses.[9]
In addition, the results show that perampanel decreased the frequency
of both complex partial seizures and secondarily generalised
seizures.[10] In a third analysis of the pooled trial data, patients
with uncontrolled partial onset seizures taking any of the five most
commonly-used AEDs with perampanel as an add-on therapy experienced a
reduction in their seizure frequency. Patients generally received
additional benefit from increased doses of perampanel.[11]

Perampanel was generally well tolerated; most adverse events were
mild/moderate.

About 307[8]

The 307 study (n=1,218) was designed to evaluate safety,
tolerability, and seizure outcome data during long-term treatment
with once-daily adjunctive perampanel (up to 12 mg/day) in people
with refractory partial onset seizures. It was an open-label
extension (OLE) study for people completing the double-blind phase of
three pivotal Phase III trials (studies 304, 305, and 306).

The study consisted of two phases: an open-label treatment phase
(including a 16-week conversion period and a planned 256-week
maintenance period) and a 4-week follow-up phase. People were blindly
titrated during the Conversion Period to their individual maximum
tolerated dose (maximum 12 mg/day). Adverse events (AEs) were
monitored throughout the study and seizure frequency recorded. The
interim data cut-off date for analyses was 1 December 1 2010.

At the interim cut-off date, 1186 patients were in the safety
analysis set; 1089 (91.8%) patients had >16 weeks' exposure to
perampanel, 580 (48.9%) patients had >1 year of exposure, and 19
(1.6%) patients had >2 years' exposure. At the interim analysis, 840
(70.8%) patients remained on perampanel treatment. The large majority
of patients (n=1084 [91%]) were titrated to 10 mg or 12 mg/day.
Median (range) duration of exposure was 51.4 (1.1-128.1) weeks.

In the ITT analysis set (n=1207), the frequency of all seizures
decreased over the first 26 weeks of perampanel treatment in patients
with at least 26 weeks' exposure to perampanel (n=1006 [83.3%]); this
reduction was maintained in patients with at least one year of
exposure (n=588 [48.7%]). The overall median percent changes in
seizure frequency in patients included in each 13-week interval of
perampanel treatment were -39.2% for weeks 13-26 (n=1114), -46.5% for
Weeks 40-52 (n=731), and 58.1% for Weeks 92-104 (n=59). Overall
responder rates in patients included in each 13-week interval of
perampanel treatment were 41.4% for Weeks 13-26 (n=1114), 46.9% for
Weeks 40-52 (n=731) and 62.7% for weeks 92-104 n=59). During the
blinded conversion period, the reduction in seizure frequency in
patients previously randomised to placebo (-42.4%, n=369) was similar
to that in patients previously randomised to perampanel (-41.5%,
n=817).

Treatment-emergent AEs were reported in 87.4% of patients. The
most frequent were dizziness (43.9%), somnolence (20.2%), headache
(16.7%), and fatigue (12.1%). Serious AEs were reported in 13.2% of
patients.

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.[12],[13] Epilepsy is a
chronic disorder of the brain that affects people of all ages. It is
characterised by abnormal discharges of neuronal activity causing
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:

- 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 generalisation, in adults, adolescents and children aged six years and above.
(Zonegran is under license from the originator Dainippon Sumitomo Pharma)
- Zebinix(R) (eslicarbazepine acetate) as adjunctive therapy in adult patients
with partial onset seizures, with or without secondary generalisation. (Zebinix is
under license from BIAL)
- Inovelon(R) (rufinamide) for the adjunctive treatment of seizures associated
with Lennox-Gastaut Syndrome in patients >4 years (Rufinamide was originally developed
by Novartis)
- Fycompa(R) (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

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

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

References

1. SPC Fycompa (updated November 2012). Available at:
http://www.medicines.org.uk/emc/medicine/26951/
[http://www.medicines.org.uk/emc/medicine/26951 ] [Accessed September
2013]

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

3. ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering
Epilepsy Care in Europe 2010. Available at; http://www.ilae.org/Visit
ors/Documents/ILAEAnnual-Report2010Final_000.pdf (Accessed September
2013)

4. García-Ramos R, et al. FEEN: Informe sociosanitario FEEN sobre
la epilepsia en España. Neurología. 2011;26:548-55. http://www.elsevi
er.es/sites/default/files/elsevier/eop/S2173-5808(11)00042-3.pdf
(Accessed September 2013)

5. Krauss GM. et al. Randomized phase III study 306: Adjunctive
perampanel for refractory partial-onset seizures. Neurology 2012;
78:1408-1415

6. French JA. Adjunctive perampanel for refractory partial-onset
seizures: randomized phase III study 304. Neurology 2012;79:589-596

7. French JA et al. Evaluation of adjunctive perampanel in
patients with refractory partial-onset seizures: Results of
randomized global phase III study 305. Epilepsia 2012:1-9

8. Krauss GL et al. Perampanel, a selective, noncompetitive
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
antagonist, as adjunctive therapy for refractory partial-onset
seizures: interim results from phase III, extension study 307.
Epilepsia, 2013;54(1):126-34.

9. Ben-Menachem E,Krauss GL, Noachtar S et al. Abstract presented
at ECE 2012

10. Steinhoff BJ, Gauffin H, McKee P et al. Abstract presented at
ECE 2012

11. Trinka E, Straub H, Squillacote D et al. Abstract presented at
ECE 2012

12. Epilepsy in the WHO European Region: Fostering Epilepsy Care
in Europe.
http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf
[Accessed September 2013]. 13. Pugliatti M, et al. Epilepsia 2007:
48(12) 2224-2233.

13. Pugliatti M, et al. Epilepsia 2007: 48(12) 2224-2233.

Date of preparation: January 2014 Job code: Perampanel-UK2142

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

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