EMA Accepts EISAI’S License Extension Application for Zonegran (zonisamide) in Epilepsy

HATFIELD, England, July 28, 2011 -

Eisai today announced that the European Medicines Agency (EMA) has accepted for review their application to extend the use of Zonegran (zonisamide) as monotherapy for newly diagnosed epilepsy patients with partial seizures, with and without second generalisation.

Zonisamide is a second generation anti-epileptic drug with multiple mechanisms of action, with a chemical structure unrelated to other anti-epileptic drugs, and with pharmacokinetic properties allowing a once daily regimen. It is approved in the European Union as an adjunctive therapy in the treatment of partial seizures (with or without secondary generalisation) in adults with epilepsy.^[1]

Epilepsy is one of the most common neurological conditions in the world, affecting approximately 8 in 1,000 people in Europe.^[2] There is an estimated six million people living with epilepsy in Europe^[3] and estimated 50 million people worldwide.^[4]

The efficacy and safety of zonisamide as monotherapy has been demonstrated in a double-blind, randomised, multicentre study which compared the efficacy and safety of once-daily zonisamide with twice-daily controlled release carbamazepine (CBZ) (Tegretol^® retard) as monotherapy in 583 adults with newly diagnosed partial epilepsy.  The study’s primary endpoint was the proportion of seizure-free patients at 6 months (per protocol population). The results of the study showed that zonisamide was effective and well tolerated in newly diagnosed epilepsy patients when used as monotherapy.^[5]

“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 Dr Bettina Bauer, Head of EU Epilepsy Business Unit, Eisai Europe; “If approved as monotherapy zonisamide will offer newly diagnosed epilepsy patients a new option to help improve their seizure control.”

About Zonegran (zonisamide)

Zonisamide is licensed as adjunctive therapy in the treatment of partial seizures (with or without generalization) in adults with epilepsy.  It has a broad spectrum of anti-epileptic modes of action and has no appreciable effects on steady-state plasma concentrations of other anti-epileptic drugs, such as phenytoin, carbamazepine, and valproate.^[1]

Zonisamide is available in 25mg, 50mg, and 100mg capsule strengths. 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.

In the monotherapy trial the dosing was once-daily both during titration and at the target dose. The starting dose was 100mg once-daily in the evening and was up-titrated every two weeks; up to an initial target dose of 300 mg/day zonisamide or 600 mg/day carbamazepine. Subjects treated with zonisamide were more likely to experience loss of appetite (7.8% versus 1.7%) and weight loss (6.8% versus 0%); 13.2% of subjects lost ≥10% of their body weight, and 0.7% lost ≥20%. There were more reports of psychiatric disorders (9.3% versus 4.7%), and fewer reports of dizziness (3.9% versus 7.7%) and rash (2.1% versus 4.3%) in subjects treated with zonisamide compared to those treated with carbamazepine. The most common adverse events were headache (ZNS: 10.3%; CBZ: 12.3%), decreased appetite (ZNS: 7.8%; CBZ: 1.7%), somnolence (ZNS: 6.0%; CBZ: 7.7%), dizziness (ZNS: 3.9%; CBZ: 7.7%), weight decreased (ZNS: 6.8%; CBZ: 0%), fatigue (ZNS: 4.6%; CBZ: 4.0%), rash (ZNS: 2.1%; CBZ: 4.3%) and pyrexia (ZNS: 3.9%; CBZ: 4.0%). ^[1]

Zonisamide is currently being investigated in paediatrics to assess the safety and efficacy for children and adolescents with partial onset seizures treated with one or two other anti-epileptic drugs.

About Epilepsy

Epilepsy is one of the most common neurological conditions in the world, affecting approximately 8 in 1,000 people in Europe.^[2] There is an estimated six million people living with epilepsy in Europe^[3] and estimated 50 million people worldwide.^[4]

Epilepsy is characterised by abnormal firing of impulses from nerve cells in the brain causing seizures. Depending on the seizure type, seizures may be limited to one part of the body, or may be generalised to involve the whole body. Patients may also experience abnormal sensations, altered behaviour or altered consciousness.

Epilepsy is a disorder with many possible causes but often the cause of epilepsy is unknown. However, anything that disturbs the normal pattern of neuron activity - from illness to brain damage to tumours, can lead to seizures.^[6]

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 anti-epileptic drugs (AEDs) is a major strategic area for Eisai in the European market.

In Europe, Eisai currently has three marketed treatments including:

• Zonegran^® (zonisamide) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalization.
• Zebinix^® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalization. (Zebinix is under license from BIAL)
• Inovelon^® (rufinamide) for adjunctive treatment, 4 years and older of seizures associated with Lennox-Gastaut Syndrome.

About Eisai

Eisai is one of the world’s leading R&D-based pharmaceutical companies and has defined its 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, multiple sclerosis, neuropathic pain, epilepsy, depression
• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc and supportive cancer therapies; pain relief, nausea
• Vascular/Immunological reaction including: acute coronary syndrome, atherothrombotic disease, severe sepsis, rheumatoid arthritis, psoriasis, Crohn’s disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, we employ 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, Hungary and Slovakia.

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

References

1. Eisai Ltd. (2005). Zonegran Summary of Product Characteristics

2. Pugliatti M et al. Estimating the cost of epilepsy in Europe: A review with economic modeling. Epilepsia 2007: 48(12) 2224 - 2233

3. ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe 2010. Available from; www.ilae-epilepsy.org/Visitors/Documents/EUROReport160510.pdf (Accessed June 2011)

4. Epilepsy Society UK: www.epilepsysociety.org.uk/AboutEpilepsy/Whatisepilepsy/Epilepsy-didyouknow (Accessed June 2011)

5. Eisai. Data on file.

6. Epilepsy Research UK. What is Epilepsy? Fact sheet. Available from URL: www.epilepsyresearch.org.uk/about_us/leaflets/lflt1.htm (Accessed June 2011)

Media Enquiries: Eisai Europe Ltd, Cressida Robson, +44(0)7908-314-155, Cressida_Robson at eisai.net; Tonic Life Communications: Helen Swift/Siobhan Reilly: +44(0)207-798-9900/+44(0)207-798-9999, helen.swift at toniclc.com/siobhan.reilly at toniclc.com