Zonegran® (Zonisamide) Well Tolerated in Long-term Treatment of Children with Partial Epilepsy

HATFIELD, England, April 22, 2014 /PRNewswire/ --

Zonegran^® (zonisamide) is well tolerated and efficacious when used as an adjunctive (add-on) treatment for partial epilepsy, with or without secondary generalisation, in children aged between 6-17 years for at least one year, according to the results of a new study published today in Epilepsia. The results of this study also showed that zonisamide was not associated with any unexpected safety issues or detrimental effects on children's growth and development.^[1] Zonisamide is a second generation anti-epileptic drug (AED) with multiple mechanisms of action and a chemical structure unrelated to any other AEDs.^[2]

It is estimated that there are approximately 0.9 million children and adolescents living with active epilepsy in Europe.^[3] Epilepsy in children often presents major challenges such as developmental and behavioural problems, resulting 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.^[4]

"Unfortunately, more than a fourth of children with epilepsy remain refractory to treatment," pointed out Professor Renzo Guerrini from the Children's Hospital Anna Meyer-University of Florence, Italy. "There is still a need for additional treatment options. The results of this 1-year open-label extension of a randomised-controlled study of zonisamide are therefore particularly welcomed and zonisamide could be a valuable treatment option for children with partial epilepsy."  

The study was an open label extension of a phase III, double-blind, randomised, placebo-controlled, multicentre trial. It set out to assess the long-term safety/tolerability and explore the long-term maintenance of efficacy of adjunctive zonisamide in 144 children aged 6-18 years from 10 European countries. Patients started with a double-blind transition period (2-11 weeks), during which patients on zonisamide continued at the same dose and those on placebo switched to zonisamide 1mg/kg/day, up-titrated to 8mg/kg/day to a maximum of 500mg/day. During the subsequent open label period (45-57 weeks), zonisamide dosing was adjusted according to tolerability and response. Tolerability, efficacy, growth and development assessments were made throughout the study.^[1]

The results of the study showed a low incidence of serious treatment-emergent adverse events (TEAEs) (2.1%) and TEAEs leading to discontinuation from the study (2.8%). During the open-label period, 56.3% of patients were classified as responders to treatment and 11.1% achieved seizure freedom. Tanner staging (a scale of physical development in children, adolescents and adults) and skeletal development were as expected for the age range of children in the study. Changes were minimal for the Child Behaviour Checklist (a widely used method of identifying problem behavior in children) and for school performance scores. Most of the children studied were 'much improved'/'very much improved' based on physician (73.8%) and parent/guardian (75.4%) global impressions of change. The results of the Controlled Oral Word Association Test (COWAT), an evaluation that measures the verbal fluency of an individual, and letter fluency scores, showed no evidence of impairment with zonisamide treatment.^[1]

Zonisamide was approved in Europe in 2005 as an adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults. In July 2012, the EC approved zonisamide as monotherapy in the treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy.^[2] The use of the adjunctive zonisamide in the treatment of partial seizures (with or without secondary generalisation) in children aged six years and above was approved by the European Commission in October 2013.

The zonisamide paediatric licence was based on Study 312 (CATZ) published in Epilepsia in July 2013.^[5] These data from a double-blind, randomised, multicentre, placebo-controlled Phase III study, showed that significantly more patients aged six to 17 responded positively to treatment with zonisamide (50%) versus treatment with placebo (31%), p=0.0044.^[5] Safety and tolerability assessments showed that the overall incidence of TEAEs was similar for zonisamide versus placebo and that there were low rates of serious TEAEs in both groups.^[5]

The continued development of zonisamide underscores Eisai's human health care (hhc) 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.^[2] 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] Zonisamide is one of only four AEDs with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures.^[6]

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 100mg daily and thereafter the dose may be increased at weekly intervals, in increments of up to 100mg.^[2]

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

About Epilepsy  

Epilepsy is one of the most common neurological conditions in the world.^[7] 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:

• 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
• Inovelon^® (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients ≥4 years. (Rufinamide was originally developed by Novartis)
• Zebinix^® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial onset seizures, with or without secondary generalisation. (Zebinix is under license from BIAL)
• Zonegran^® (zonisamide) as monotherapy in adults 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)

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 management
• 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. 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. doi: 10.1111/epi.12548 

2. Eisai Ltd 2013. Zonegran summary of product characteristics (last updated October 2013) https://www.medicines.org.uk/emc/medicine/16240/SPC/Zonegran+25%2c+50%2c+100+mg+Hard+Capsules/

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

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

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. Glauser T. et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013 Mar;54(3):551-63 

7. 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: April 2014
Job code: Zonegran-UK2525