Eisai's Zonegran® (Zonisamide) Approved for Use in Children with Partial Epilepsy in UK and Netherlands

   Eisai's Zonegran® (Zonisamide) Approved for Use in Children with Partial
                        Epilepsy in UK and Netherlands

  PR Newswire

  HATFIELD, England, October 3, 2013

HATFIELD, England, October 3, 2013 /PRNewswire/ --

    New paediatric epilepsy treatment option available following European
                         Commission license extension

Zonegran ^® (zonisamide) is now available for the treatment of partial
epilepsy in children and adolescents in the United Kingdom (UK) and the
Netherlands. This follows the paediatric license extension approval by the
European Commission. Zonisamide, a novel anti-epileptic drug (AED) with
multiple mechanisms of action and a chemical structure unrelated to any other
AED, 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. ^[1]

Epilepsy is a serious neurological disorder in childhood and has long-term
implications for health and well-being. ^[2] The estimated number of children
and adolescents in Europe with active epilepsy is 0.9 million, ^[3] with
around 63,000 living in the UK. ^[4] Although epilepsy is common among this
age group, only two thirds will achieve seizure control and many will require
additional AEDs to improve seizure control. ^[5]

"It is pleasingthat Zonegran has now been licensed to be prescribed for
children, as new options for young people with epilepsy are needed
desperately," said Professor Helen Cross, Great Ormond Street Hospital and
Young Epilepsy. "Epilepsyaffects all aspects of children and their family's
lives. New, effective and well tolerated treatments that can be used in
children that achieve a balance between stopping seizures and keeping side
effects to a minimum are welcomed by doctors, patients and parents."

The zonisamide paediatric approval was based on Study 312 (CATZ) published in
Epilepsia in July 2013. ^[6] These data from a double-blind, randomised,
multicentre, placebo-controlled Phase III study, showed that significantly
more patients responded positively to treatment with zonisamide (50%) versus
treatment with placebo (31%), p=0.0044. ^[ ^6 ^] The overall incidence of
treatment-emergent adverse events (TEAEs) was similar for zonisamide versus
placebo. ^[ ^6 ^] Zonisamide is also indicated as monotherapy in the treatment
of partial seizures, with or without secondary generalisation, in adults with
newly diagnosed partial epilepsy.

"As a research-based pharmaceutical company with a particular focus on
epilepsy, we are not only committed to bringing innovative new therapies to
market, but also ensuring that we maximise the clinical benefits of our
currently licensed products," said Patrick Standen, Brand Director, Eisai
EMEA. "We hope that the availability of Zonegran for use in children and
adolescents will help many more people with epilepsy across the UK and the
Netherlands."

The continued development of zonisamide underscores Eisai's human health care
mission, the company's commitment to innovative solutions in prevention, cure
and care for the health and wellbeing 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 EMEA than any other company.

Notes to Editors

About Zonegran (zonisamide)

Zonisamide is licensed in Europe as monotherapy in the treatment of partial
seizures, with or without secondary generalisation, in adults with newly
diagnosed epilepsy. Zonisamide is also indicated as adjunctive therapy in the
treatment of partial seizures, with or without secondary generalisation, in
adults, adolescents and children aged six years and above. It has a broad
spectrum of anti-epileptic modes of action and has no appreciable effects on
steady-state plasma concentrations of other AEDs, such as phenytoin,
carbamazepine and valproate. Zonegran is one of only four AEDs with level A
efficacy/effectiveness evidence as initial monotherapy for adults with partial
onset seizures. ^[7]

Zonisamide is available in 25mg, 50mg, and 100mg capsule strengths. The
recommended daily dose for monotherapy use is 100mg once daily. In the third
and fourth weeks the dose may be increased to 200mg daily and then increased
to 300mg daily after the next two weeks.The recommended initial daily dose for
adjunctive use is 50mg in two divided doses. After one week the dose may be
increased to 100 mg daily and thereafter the dose may be increased at weekly
intervals, in increments of up to 100 mg.

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

Phase III Study 312 (CATZ) ^[ ^6 ^]

Study 312 was a double-blind, randomised, placebo-controlled, multi-centre
study (n=207) to assess the efficacy and safety of adjunctive zonisamide in
paediatric partial onset seizures (6 - 17 years old). In the study, children
with partial epilepsy, receiving one or two antiepileptic drugs, were
randomised to receive either adjunctive zonisamide or placebo. Zonisamide was
initiated at 1 mg/kg/day, titrated to a target dose of 8 mg/kg/day over eight
weeks (one down-titration permitted) and maintained for 12 weeks. The primary
efficacy end point of the study was the proportion of responders (defined as a
≥50% seizure frequency reduction from baseline) during the 12-week maintenance
period.

The responder rates were found to be 50% for zonisamide vs. 31% for placebo (p
= 0.0044). The overall incidence of treatment emergent adverse events (TEAEs)
was similar for zonisamide (55.1%) vs. placebo (50.0%), with low rates of
serious TEAEs in both arms of the study (3.7% zonisamide vs. 2.0% placebo) and
TEAEs leading to withdrawal (0.9% vs. 3.0%).

Results of the Phase III study were published in July 2013 in Epilepsia ^® .

About Epilepsy

Epilepsy is one of the most common neurological conditions in the world. ^[8]
There are an estimated six million people who live with epilepsy in Europe,
and an estimated 50 million people with the condition worldwide. 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:

  *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. (Rufinamide
    was originally developed by Novartis)
  *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 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. Eisai Ltd 2013. Zonegran Summary of Product Characteristics [
http://www.medicines.org.uk/emc/medicine/16240/SPC/Zonegran+25%2c+50%2c+100+mg+Hard+Capsules
] (last updated February 2013)

2. Meeraus WH, et al. Childhood epilepsy recorded in primary care in the UK.
Arch Dis Child 2013;98:195 - 202.

3. Forsgren L. et al. The epidemiology of epilepsy in Europe  -  a
systematic review. European Journal of Neurology.2005 12(4) 245-253)

4. Epilepsy prevalence, incidence and other statistics. Joint Epilepsy
Council, September 2011

5. Epilepsy Society. Medication for children. [
http://www.epilepsysociety.org.uk/AboutEpilepsy/Treatment/Medicationforchildren
] [Accessed 16 July 2012].

6. Guerrini R. et al. A randomized, phase III trial of adjunctive zonisamide
in pediatric patients with partial epilepsy. Epilepsia 2013

7. Glauser T. et al. Updated ILAE evidence review of antiepileptic drug
efficacy and effectiveness as initial monotherapy for epileptic seizures and
syndromes.

8. 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: October 2013

Job code: Zonegran-UK2504

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