Epilepsy Treatment Zonegran® (Zonisamide) Receives Reimbursement in Spain as Monotherapy for Adults and Adjunctive Therapy for Children and Adolescents

HATFIELD, England, February 19, 2014 /PRNewswire/ --

Zonegran^® (zonisamide) has received reimbursement approval from The Spanish Directorate General of Pharmacy and Health Products, part of the Spanish Ministry of Health, 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 epilepsy in children and adolescents from six years old. The antiepileptic drug (AED) has been promoted in Spain by Eisai's partner, Esteve, since December 2013. Once-daily zonisamide is a second generation AED with multiple mechanisms of action and a chemical structure unrelated to any other AEDs.^[1]

For people with newly diagnosed epilepsy, monotherapy is the preferred option for managing their condition as this reduces the potential for adverse drug interactions and encourages treatment compliance.^[2] Epilepsy in children often presents major challenges such as developmental and behavioural problems that result in educational underachievement and a lack of self-esteem. These issues, which are frequently manifested in an attention deficit disorder, withdrawal, anxiety or depression, have a negative impact on both the child and their family.^[3]

"The availability of zonisamide in Spain as monotherapy in adults and the widened indication for its use as adjunctive therapy in children over the age of six and beyond is welcome and will provide a new treatment option for doctors and patients," commented Dr Pedro Serrano-Castro, Department of Neurology and Neurophysiology, Hospital Torrecardenas, Spain.

"The extension of the Zonegran indication provides doctors with an effective and well-tolerated additional tool for the treatment of a condition that still poses many unsolved therapeutic challenges," commented Dr. Pere Fernández, Director of Medical Department & Health Innovation at Esteve.

Epilepsy is one of the most common neurological conditions in the world,^[4] with an estimated 400,000 people who currently live with epilepsy in Spain alone.^[5] The successful treatment of partial onset seizures (the most common type of epilepsy) remains a significant challenge and up to 30% of patients fail to achieve seizure freedom with existing AEDs.^[6]

The efficacy and safety of zonisamide as monotherapy has been demonstrated in a double-blind, randomised, multicentre study of 583 newly diagnosed adult partial epilepsy patients, which compared the efficacy and safety of once-daily zonisamide with twice-daily controlled release carbamazepine as monotherapy. The study's primary endpoint was the proportion of seizure-free patients at six months. Zonisamide demonstrated high response rates for achieving seizure freedom in newly diagnosed patients with epilepsy,^[7] similar to controlled release carbamazepine. In the majority of patients, seizure freedom was achieved at the target dose of 300 mg. Zonisamide was considered non-inferior to carbamazepine, was well tolerated and had no apparent safety concerns after one year of treatment at doses ranging from 300 to 500 mg/day.

The zonisamide paediatric approval was based on Study 312 (CATZ) published in Epilepsia in July 2013.^[8] 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]

"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. The new extended monotherapy and adjunctive therapy indication for Zonegran provides an alternative treatment option to help improve seizure control." said Dr. Javier Sánchez, Medical Manager, Eisai Spain. "Zonegran is one of only six AEDs available as monotherapy, allowing doctors to tailor treatment to individual patient needs."

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 wellbeing of people worldwide. Eisai is committed to the therapeutic area of epilepsy and addressing the unmet medical needs of people with epilepsy and their families. Eisai is proud to market currently 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.^[1] 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.^[1] 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.^[1]

For paediatric patients the starting dose is 1 mg/kg once a day with increments of 1 mg/kg /day at weekly intervals, across weeks 2 to 8, to reach a maintenance dose of 6 to 8 mg/kg once a day for patients weighing 20 to 55 kg or 300 to 500 mg once a day for patients above 55 kg.

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

About Epilepsy

Epilepsy is one of the most common neurological conditions in the world.^[10] 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 adults, adolescents and children aged six years and above 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

About Esteve

Esteve is a leading pharmaceutical chemical group based in Barcelona, Spain. Since it was founded in 1929, Esteve has been firmly committed to excellence in healthcare, dedicating efforts to innovative R&D of new medicines for unmet medical needs and focusing on high science and evidence-based research. Esteve has a strong partnership approach to drug discovery, development and commercialisation. The company works both independently and in collaboration to bring new, differentiated best-in-class treatments to patients who need them. The company currently has a team of about 2300 professionals, and has subsidiaries and production facilities in several European countries, USA, China and Mexico.

For further information, please visit http://www.esteve.com

References

1. 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

2. St. Louis, K. Rosenfeld. W. Bramley, T. Antiepileptic Drug Monotherapy: The Initial Approach in Epilepsy Management (2009) &(2): 77-72

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

4. ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe 2010. Available at; http://www.ilae.org/Visitors/Documents/ILAEAnnual-Report2010Final_000.pdf (Accessed Feb 2013)

5. García-Ramos R, et al. FEEN: Informe sociosanitario FEEN sobre la epilepsia en España. Neurología. 2011;26:548-55. http://www.elsevier.es/sites/default/files/elsevier/eop/S2173-5808(11)00042-3.pdf (Last accessed May 2013)

6. Kwan P, Brodie MJ Early identification of refractory epilepsy. New England Journal of Medicine 2000; 342:314-9

7. Baulac, M. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurology (2012), 11 (7) 579 - 588

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

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

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: February 2014
Job code: Zonegran-UK2509