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

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 pleasing that 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. "Epilepsy affects 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