Eisai Appalled by the German Federal Joint Committee's Decision on Innovative Antiepileptic Drug Fycompa® (perampanel)

Eisai Appalled by the German Federal Joint Committee's Decision on Innovative
                   Antiepileptic Drug Fycompa® (perampanel)

  PR Newswire

  FRANKFURT, Germany and HATFIELD, England, March 7, 2013

FRANKFURT, Germany and HATFIELD, England, March 7, 2013 /PRNewswire/ --

The German Federal Joint Committee (G-BA), the decision-making body of the
self-governing medical system in Germany, today announced that it considers
the additional benefit of Fycompa ^® (perampanel) unproven when compared to
two other treatments as defined by the G-BA. ^[ ^1] Perampanel is indicated as
an adjunctive treatment of partial-onset seizures with or without secondarily
generalised seizures in patients with epilepsy aged 12 years and older. ^[ ^2]
Perampanel is the first in an entirely new class of innovative treatment for
uncontrolled partial epilepsy with a novel mechanism of action that is
different from all other anti-epileptic drugs (AEDs).

Eisai is appalled by the G-BA's ruling. This decision follows the German
Institute for Quality and Efficiency in Health Care (IQWiG) assessment,
published 17 December 2012 which reported that the benefit of perampanel is
unproven based on methodological grounds. The company believes that the G-BA
failed to adequately interpret the proven patient-relevant benefits
substantiated in the submitted benefit dossier and to responsibly recognise
the innovative nature of the new drug in a clinical setting with a highly
unmet medical need.

Eisai diligently developed the benefit dossier following scientific advice
from the G-BA. In addition, Eisai provided further evidence in a written
statement preceding the G-BA Oral Hearing on 29 January 2013, and re-iterated
the additional benefit perampanel provides to patients, especially to patients
who require new options to help manage their seizures. Eisai maintains that
the submitted benefit dossier contains a methodologically robust comparative
analysis against the appropriate comparative therapy, lamotrigine, as defined
by the G-BA. On the advice of the G-BA, Eisai also performed an indirect
analysis using published clinical data for lamotrigine. Eisai strongly
believes that it has provided compelling evidence to demonstrate the
additional benefit of perampanel.

"I cannot understand the decision by the G-BA, from my personal clinical
experience, it is definitely certain that perampanel provides additional
benefit for patients with partial onset seizures. I can see this additional
benefit in my clinical practice every day. There are still a large number of
patients requiring new and innovative treatments like perampanel to help them
manage their seizures," said Professor Bernhard Steinhoff from
Epilepsiezentrum Kork, Kehl-Kork, Germany

Nick Burgin, European Director of Market Access, Eisai added; "We believe the
G-BA decision failed to take into account the patient need for new innovative
treatments. Further they did not acknowledge the patient-value of perampanel
that was demonstrated in the comprehensive analyses submitted. This is a clear
example where this process of evaluation does not reflect the additional
patient benefit seen in clinical experience in an area of high unmet need."

In Germany, approximately one out of 200 people has epilepsy equating to an
estimated 400,000 people in the country living with the condition. ^[3]
Epilepsy is one of the most common neurological conditions in the world. ^[4]
The successful treatment of partial-onset seizures remains a challenge as over
30% of patients do not achieve seizure freedom despite appropriate therapy
with anti-epileptic drugs. ^[5]

Many of these patients have exhausted other treatment options. The clinical
experience with perampanel shows that it reduces the frequency of both complex
partial and secondarily generalised in these difficult to treat patients. ^[
^6]

Perampanel was first launched in Europe in Germany and the UK in September
2012. It has been well received by both patients and doctors. It is the first
and only licensed AED to selectively target AMPA receptors which play a
critical role in causing seizures. ^[7] It blocks the effects of glutamate,
which can trigger and maintain seizures.

Perampanel was approved by the European Commission on 23 July 2012. The FDA
approved perampanel for use in the US on 22 October 2012. In Europe, it is
currently available in the UK, Denmark, Germany, Austria, Sweden, Norway and
Switzerland.

The development of perampanel 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 well-being of people worldwide.
Eisai is committed to the therapeutic area of epilepsy and addressing the
unmet medical needs of patients with epilepsy and their families. Eisai is
proud to currently market more epilepsy products in Europe than any other
company.

Notes to Editors

About Perampanel

Perampanel is licensed in Europe Union as an adjunctive treatment for people
aged 12 years and older with partial-onset seizures, with or without
secondarily generalised seizures. ^[ ^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 signaling including epilepsy,
neurodegenerative disorders, movement disorders, pain and psychiatric
disorders. ^[ ^2 ^]

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

About the Perampanel Pooled Data (Study 306, 305 and 304)

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.

Fifty percent responder rates were greater with perampanel 4 mg (28·5%), 8 mg
(35·3%), and 12mg (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%).

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. ^[8] In addition, the results show that
perampanel decreased the frequency of both complex partial seizures and
secondarily generalised seizures. ^[ ^6 ^] 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. ^[9]

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

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 with the condition worldwide. ^[10] ^, ^[11] 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 Europe 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
and Russia (EMEA).

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

  *Zonegran ^® (zonisamide) as monotherapy and adjunctive therapy in adult
    patients with partial-onset seizures, with or without secondary
    generalisation. (Zonegran is under license from the originator Dainippon
    Sumitomo Pharma)
  *Zebinix ^® (eslicarbazepine acetate) as adjunctive therapy in adult
    patients with partial-onset seizures, with or without secondary
    generalisation. (Zebinix is under license from BIAL)
  *Inovelon ^® (rufinamide) for the adjunctive treatment of seizures
    associated with Lennox-Gastaut Syndrome in patients >4 years
  *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

About Eisai

Eisai recently expanded their UK Hatfield commercial, research and
manufacturing facility which now supports the company's growing EMEA business.

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 11,000 people worldwide. In Europe, Eisai
undertakes sales and marketing operations in over 20 markets, including the
United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland,
Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic,
Slovakia, the Netherlands, Belgium, Luxembourg, the Middle East and Russia.

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

References

1. http://www.g-ba.de/informationen/beschluesse/1664/ (Accessed March 2013)

2. Fycompa. Summary of Product Characteristics. August 2012

3. Pfäfflin, M. und May, T. Wieviele Patienten mit Epilepsien gibt es in
Deutschland und wer behandelt sie? Neurol Rehabil,2000; 6, (2) 77-81.

4. ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care
in Europe 2010. Available at;
http://www.ilae.org/Visitors/Documents/ILAEAnnual-Report2010Final_000.pdf
(Accessed June 2011)

5. Brodie MJ et al, Neurology 2012; 78:1548-1554

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

7. Rogawski MA. Epilepsy Currents 2011;11:56-63

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

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

10. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe
http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [Accessed
August 2012]

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



Date of preparation: March 2013

Job code: Perampanel - UK2119

Contact: Media Enquiries: Eisai Europe Ltd, Cressida Robson / Charlotte
Andrews, +44(0)7908 314 155/+44(0)7947 231 513, Cressida_Robson@eisai.net,
Charlotte_Andrews@eisai.net ; Tonic Life Communications, Moira Gitsham /
Nicola Lilley, +44 (0) 207 798 9992/+44(0)20 7798 9905,
moira.gitsham@toniclc.com / nicola.lilley@toniclc.com /
eisaiepilepsy@toniclc.com