Zonegran® Paediatric Pivotal Phase III Data Published in Epilepsia

HATFIELD, England, July 10, 2013 /PRNewswire/ --

Results from a Phase III study of adjunctive Zonegran (zonisamide) in patients aged 6-17 years with partial epilepsy is published today in leading clinical and research epilepsy publication Epilepsia.^[1] Zonisamide is a second generation AED with multiple mechanisms of action and a chemical structure which is unrelated to any other AEDs.^[2] Once-daily Zonegran is currently 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 generalisation) in adults.

The estimated number of children and adolescents in Europe with active epilepsy is 0.9 million.^[3] 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.^[4] 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.^[5]

"Epilepsy has a high negative impact on both children and their families and there is a pressing need for new treatment options as too many children still experience breakthrough seizures," points out study author Professor Renzo Guerrini from the Children's Hospital Anna Meyer-University of Florence, Italy.  "Some children may need to be on multiple medications and so it is important to have a balance between stopping seizures and keeping treatment related side effects to a minimum."

In the double-blind, placebo-controlled, multicentre trial (n=207), children with partial epilepsy, receiving one or two antiepileptic drugs, were randomised to receive either adjunctive once-daily zonisamide or placebo. 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%).

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 patients with epilepsy and their families. Eisai is proud to currently market more epilepsy products in EMEA than any other company.

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.^[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 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

About Epilepsy

Epilepsy is one of the most common neurological conditions in the world, affecting approximately one in every one hundred people in Europe, and an estimated 50 million people worldwide.^[7],[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 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 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. Guerrini R, Rosati A, Segieth J, Pellacani S, Bradshaw K, Giorgi l. A randomized, phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy. Epilepsia 2013 

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

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

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

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

6. 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]

7. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [Accessed 10 April 2012].

8. Pugliatti M, et al. Epilepsia 2007: 48(12) 2224 - 2233.

Date of preparation: July 2013

Job code: Zonegran-UK2490