Eisai's Epilepsy Treatment Zonegran® (Zonisamide) Approved for Use in Children and Adolescents in France

Hatfield, England (ots/PRNewswire) -

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

On the 9 February, the Transparency Commission of the French
National Authority for Health (HAS) published its advice on
Zonegran(R) (zonisamide) in its new indication for the treatment of
partial seizures in adolescents and children from 6 years of age.[1]
Zonisamide, a novel anti-epileptic drug (AED) with a multimodal
mechanism of action and a chemical structure unrelated to any other
AED, was already indicated in Europe 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. Now, adolescents and children from 6 years
of age will be able to benefit from this treatment as an adjunctive
therapy.

Epilepsy is a serious neurological disorder in childhood and has
long-term implications for health and well-being.[2] Around 450,000
people in France live with the condition, with over 100 new cases
diagnosed each day.[3] Although epilepsy is common in paediatrics,
seizure control is only achieved in two thirds of patients and many
will require additional AEDs to decrease the seizure frequency.[4]

"New therapeutic options for young people with epilepsy are
needed, so I am delighted to see that zonisamide can now be
prescribed in France for people aged six and above," said Dr Stéphane
Auvin, Epileptologist & Child Neurology at Pediatric Neurology,
Robert Debré Children Hospital, Paris. "Epilepsy has an impact on 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 Zonegran license extension in paediatrics was granted by the
European Commission in October 2013. This paediatric approval was
based on study 312 (CATZ) published in Epilepsia in July 2013.[5] The
double-blind, randomised, multicentre, placebo-controlled Phase III
study showed that significantly more patients responded positively to
treatment with zonisamide (50%) compared to treatment with placebo
(31%), p=0.0044.[4] The overall incidence of treatment-emergent
adverse events (TEAEs) was similar in patients receiving zonisamide
compared to placebo.[4]

"As a research-based pharmaceutical company and a leader in
epilepsy, Eisai is not only committed to bringing innovative new
therapies to market, but also ensuring that we maximise the clinical
benefits of our currently licensed products," commented France
Roizen, Epilepsy Brand Lead, Eisai France. "We hope that the
availability of Zonegran for use in children and adolescents in
France will help many young people with epilepsy gain clinical
benefit from the medicine."

The continued development of zonisamide underscores Eisai's human
health care (hhc) mission, the pharmaceutical 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 pharmaceutical 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.[6] 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.[5]

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.[5]

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

Phase III Study 312 (CATZ)[4]

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 greater than or equal to50% 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 a low rate of serious adverse events in both arms of
the study (3.7% zonisamide vs. 2.0% placebo) including adverse events
leading to withdrawal (0.9% vs. 3.0%).

Phase III Study 313 (CATZ Extension)[7]

Study 313 was an open-label extension study to assess the efficacy
and safety of adjunctive zonisamide in paediatric partial onset
seizures (6-18 years old), following Phase III study 312 (CATZ). The
safety study comprised a double-blind transition period (patients
previously treated with placebo were up-titrated to a target
zonisamide dose of 8 mg/kg/day; patients previously treated with
zonisamide continued at same dose) followed by flexible, open-label
dosing (duration 45?'57 weeks). The efficacy study began with a
double-blind transition period (duration 2?'11 weeks), during which
patients already receiving zonisamide continued at same dose, while
those previously receiving placebo switched to zonisamide, initiated
at 1 mg/kg/day and up-titrated to a target of 8 mg/kg/day (maximum
500 mg/day). This was followed by an open-label period (duration
45?'57 weeks), during which zonisamide dosing could be adjusted
according to tolerability and response.

Most TEAEs were of mild or moderate intensity. Treatment-related
TEAEs were reported by 39/144 (27.1%) patients; most frequently,
decreased weight (6.3%), decreased appetite (4.2%) and headache
(2.1%). Rates of serious adverse events and adverse events leading to
discontinuation were low (2.1% and 2.8%, respectively). Efficacy
results were similar for patients who initially received placebo
(40/72; 55.6%; 95% CI, 43.4%, 67.3%) and zonisamide (41/72; 56.9%;
95% CI, 44.7%, 68.6%) before entering the open label trial. Overall,
16/144 (11.1%) patients achieved seizure freedom during open-label
period (95% CI, 6.5%, 17.4%); results being identical for patients
initially receiving placebo and zonisamide (for both populations:
8/72; 11.1%; 95% CI, 4.9%, 20.7%). Seizure frequency reduction was
maintained throughout the study; the median percentage decrease in
seizure frequency being 65.9% during open-label period.

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.[8] 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 the development and delivery of 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 use as an adjunctive treatment for partial
onset seizures, with or without secondarily generalised seizures, in patients with
epilepsy aged 12 years and older
- Inovelon(R) (rufinamide) for the adjunctive treatment of seizures associated
with Lennox-Gastaut Syndrome in patients >4 years. (Rufinamide was originally
developed by Novartis)
- 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).

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. Haute Autorité de Santé. Commission de la Transparence:
Zonegran. Updated December 2014

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

3. Sante Medecine. Épilepsie - Statistiques en France http://sante
-medecine.commentcamarche.net/contents/731-epilepsie-statistiques-en-
france . Last accessed February 2015

4. Epilepsy Society. Medication for children. http://www.epilepsys
ociety.org.uk/AboutEpilepsy/Treatment/Medicationforchildren. Last
accessed February 2015

5. Guerrini R. et al. A randomized, phase III trial of adjunctive
zonisamide in pediatric patients with partial epilepsy. Epilepsia
2013: Aug;54(8):1473-80

6. Eisai Ltd 2013. Zonegran summary of product characteristics
(last updated October 2013) https://www.medicines.org.uk/emc/history/
16240/SPC/Zonegran+25,+50,+100+mg+Hard+Capsules

7. Guerrini R, et al. Adjunctive zonisamide therapy in the
long-term treatment of children with partial epilepsy: Results of an
open-label extension of a phase III, randomised, double-blind,
placebo-controlled trial. Epilepsia. 2014:55(4):568-578

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: February 2015
Job code: Zonegran-UK2526

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

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