Eisai Gains Positive CHMP Opinion for Zonegran® (Zonisamide) Paediatric Licence Variation

HATFIELD, England, July 29, 2013 /PRNewswire/ --

Eisai announced today that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for the use of Zonegran^® (zonisamide) as a once-daily, adjunctive treatment of partial seizures (the most common form of epilepsy) with or without secondary generalisation in children aged six and above.^[1] Zonisamide is a novel anti-epileptic drug (AED) with multiple mechanisms of action and a structure which is chemically unrelated to any other AED.^[2] It is currently indicated for adjunctive treatment of partial seizures in adults and, since July 2012, the drug can also be prescribed as monotherapy in adults with newly diagnosed partial epilepsy.^[2]  

Epilepsy is a common condition in children with partial seizures being the most frequently observed seizure type.^[3],[4] The estimated number of children and adolescents in Europe with active epilepsy is 0.9 million.^[5] Only two thirds of children and young adults with epilepsy will have seizure control once a suitable AED is found for them and many children require additional AEDs (anti-epileptic drugs) to improve seizure control.^[6] Epilepsy in children often presents major challenges such as learning and behavioural problems which can result in educational underachievement. Behavioural problems that have been associated with epilepsy include hyperactivity, aggression, autistic features, depression, and low self-esteem.^[7]

Commenting on the CHMP positive opinion, Professor Helen Cross, Honorary Consultant in Paediatric Neurology at Great Ormond Street Hospital said: "There are still a large number of children with epilepsy who do not achieve seizure control and therefore may need to trial more than one anti-epileptic drug in an attempt to reduce their seizures. In children with early onset epilepsy, improving seizure control is important for a child's health and development. Any new option for treatment is welcome for doctors specializing in epilepsy to use."

The submission to extend the use of zonisamide to include children aged six years and above was based on data from the double-blind, randomised, multicentre, placebo-controlled phase III CATZ study, which showed that zonisamide is more effective than placebo, and well tolerated in paediatric epilepsy patients (6-17 years) with partial-onset seizures treated with one or two other anti-epileptic drugs.^[8]

Specifically, results showed that significantly more patients responded (> 50% seizure frequency reduction) positively to treatment with zonisamide (50.0%) versus treatment with placebo (31.0%).^[8]

"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, EMEA Brand Director, Eisai Europe Ltd. "If approved in Europe as a treatment for children aged six and above, zonisamide will offer children with epilepsy a new option to help improve their seizure control."

The continued development of zonisamide underscores Eisai's human health care 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 EMEA than any other company, and is dedicated to becoming the number one epilepsy company in Europe (by sales) by 2015, as stated in its Hayabusa plan.

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. In addition, zonisamide is also indicated as adjunctive therapy in the treatment of partial seizures (with or without generalisation) 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 AEDs, such as phenytoin, carbamazepine and valproate.^[2] Zonegran is one of only four AEDs with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures.^[9]

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.^[2]

For more information please visit: http://www.eisai.co.uk

Phase III Study 312 (CATZ)^[8]

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, affecting approximately eight in 1,000 people in Europe.^[10] There are an estimated six million people living 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 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, 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
• 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 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, and the Middle East.

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

References

1. Opinion of the Committee for Medicinal Products for Human use on a type II variation to the terms of the marketing authorsation for Zonegran, European Medicines Agency 2013

2. Eisai Ltd 2013. Zonegran Summary of Product Characteristics [http://emc.medicines.org.uk ]

3. Berg AT, Shinnar S, Levy SR, Testa FM. Newly diagnosed epilepsy in children: presentation at diagnosis. Epilepsia 1999;40:445‒452.

4. Bergin AM. Pharmacotherapy of paediatric epilepsy. Expert Opin Pharmacother 2003;4:421‒431.

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

6. http://www.epilepsysociety.org.uk/AboutEpilepsy/Treatment/Medicationforchildren

7. Sabbagh S, et al. Impact of epilepsy characteristics and behavioral problems on school placement in children. Epilepsy & Behavior 9 (2006) 573-578

8. Guerrini R. et al. A randomized, phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy. Epilepsia, 2013 doi: 10.1111/epi.12233

9. Glauser T. et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. http://www.ilae.org/Visitors/Documents/Guidelines-epilepsia-12074-2013.pdf [Accessed April 2013]

10. 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: July 2013

Job code: Zonegran-UK2473