Eisai's Epilepsy Treatment Zonegran® (Zonisamide) Approved for Use in Children and Adolescents in France

HATFIELD, England, February 18, 2015 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/U.S. JOURNALISTS 

On the 9 February, the Transparency Commission of the French National Authority for Health (HAS) published its advice on Zonegran® (zonisamide) in its new indication for the treatment of partial seizures in adolescents and children from 6 years of age.^[1] Zonisamide, a novel anti-epileptic drug (AED) with a multimodal mechanism of action and a chemical structure unrelated to any other AED, was already indicated in Europe 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. Now, adolescents and children from 6 years of age will be able to benefit from this treatment as an adjunctive therapy.

Epilepsy is a serious neurological disorder in childhood and has long-term implications for health and well-being.^[2] Around 450,000 people in France live with the condition, with over 100 new cases diagnosed each day.^[3] Although epilepsy is common in paediatrics, seizure control is only achieved in two thirds of patients and many will require additional AEDs to decrease the seizure frequency.^[4]

"New therapeutic options for young people with epilepsy are needed, so I am delighted to see that zonisamide can now be prescribed in France for people aged six and above," said Dr Stéphane Auvin, Epileptologist & Child Neurology at Pediatric Neurology, Robert Debré Children Hospital, Paris. "Epilepsy has an impact on 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 Zonegran license extension in paediatrics was granted by the European Commission in October 2013. This paediatric approval was based on study 312 (CATZ) published in Epilepsia in July 2013.^[5] The double-blind, randomised, multicentre, placebo-controlled Phase III study showed that significantly more patients responded positively to treatment with zonisamide (50%) compared to treatment with placebo (31%), p=0.0044.^[4] The overall incidence of treatment-emergent adverse events (TEAEs) was similar in patients receiving zonisamide compared to placebo.^[4]

"As a research-based pharmaceutical company and a leader in epilepsy, Eisai is not only committed to bringing innovative new therapies to market, but also ensuring that we maximise the clinical benefits of our currently licensed products," commented France Roizen, Epilepsy Brand Lead, Eisai France. "We hope that the availability of Zonegran for use in children and adolescents in France will help many young people with epilepsy gain clinical benefit from the medicine."

The continued development of zonisamide underscores Eisai's human health care (hhc) mission, the pharmaceutical 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 pharmaceutical 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.^[6] 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.^[5]

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.^[5]

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

Phase III Study 312 (CATZ)^[4]

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 a low rate of serious adverse events in both arms of the study (3.7% zonisamide vs. 2.0% placebo) including adverse events leading to withdrawal (0.9% vs. 3.0%).

Phase III Study 313 (CATZ Extension)^[7] 

Study 313 was an open-label extension study to assess the efficacy and safety of adjunctive zonisamide in paediatric partial onset seizures (6-18 years old), following Phase III study 312 (CATZ). The safety study comprised a double-blind transition period (patients previously treated with placebo were up-titrated to a target zonisamide dose of 8 mg/kg/day; patients previously treated with zonisamide continued at same dose) followed by flexible, open-label dosing (duration 45‒57 weeks). The efficacy study began with a double-blind transition period (duration 2‒11 weeks), during which patients already receiving zonisamide continued at same dose, while those previously receiving placebo switched to zonisamide, initiated at 1 mg/kg/day and up-titrated to a target of 8 mg/kg/day (maximum 500 mg/day). This was followed by an open-label period (duration 45‒57 weeks), during which zonisamide dosing could be adjusted according to tolerability and response.

Most TEAEs were of mild or moderate intensity. Treatment-related TEAEs were reported by 39/144 (27.1%) patients; most frequently, decreased weight (6.3%), decreased appetite (4.2%) and headache (2.1%). Rates of serious adverse events and adverse events leading to discontinuation were low (2.1% and 2.8%, respectively). Efficacy results were similar for patients who initially received placebo (40/72; 55.6%; 95% CI, 43.4%, 67.3%) and zonisamide (41/72; 56.9%; 95% CI, 44.7%, 68.6%) before entering the open label trial. Overall, 16/144 (11.1%) patients achieved seizure freedom during open-label period (95% CI, 6.5%, 17.4%); results being identical for patients initially receiving placebo and zonisamide (for both populations: 8/72; 11.1%; 95% CI, 4.9%, 20.7%). Seizure frequency reduction was maintained throughout the study; the median percentage decrease in seizure frequency being 65.9% during open-label period.

About Epilepsy  

Epilepsy is one of the most common neurological conditions in the world, affecting approximately eight in 1,000 people in Europe, and an estimated 50 million people worldwide.^[8] 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 EMEA in Epilepsy  

Eisai is committed to the development and delivery of 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)
• Zonegran^® (zonisamide) 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 generalisation, in adults, adolescents and children aged six years and above. (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).

About Eisai Co., Ltd. 

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. 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 our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology. 

As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.

For more information about Eisai Co., Ltd., please visit http://www.eisai.com .

References 

1. Haute Autorité de Santé. Commission de la Transparence: Zonegran. Updated December 2014 

2. Meeraus WH, et al. Childhood epilepsy recorded in primary care in the UK. Arch Dis Child 2013;98:195-202 

3. Sante Medecine. Épilepsie - Statistiques en France http://sante-medecine.commentcamarche.net/contents/731-epilepsie-statistiques-en-france. Last accessed February 2015 

4. Epilepsy Society. Medication for children. http://www.epilepsysociety.org.uk/AboutEpilepsy/Treatment/Medicationforchildren. Last accessed February 2015 

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. 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 

7. 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. 2014:55(4):568-578

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: February 2015
Job code: Zonegran-UK2526