EMA Accepts Licence Extension Application For Use Of Eisai's Adjunctive Treatment Zonegran® (zonisamide) In Children With Partial Onset Epilepsy

HATFIELD, England, July 11, 2012 /PRNewswire/ -- The European Medicines Agency (EMA) has accepted the submission by Eisai of an application to extend the use of adjunctive epilepsy treatment Zonegran® (zonisamide) in the treatment of partial seizures (with or without secondary generalisation) to include children aged six years and above. A decision on this new licence extension application is expected in September 2012. 

This submission 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.[1]

Specifically, results showed that significantly more patients responded positively to treatment with zonisamide (50.5%) versus treatment with placebo (31.0%).[1] Safety and tolerability assessments showed that the overall incidence of treatment-emergent adverse events (TEAEs) was similar for zonisamide (55.1%) versus placebo (50.0%). There were low rates of serious TEAEs in the zonisamide and placebo groups (3.7% vs 2.0%) and TEAEs leading to withdrawal from the study (0.9% vs 3.0%).[1]

Zonisamide is a second generation anti-epileptic drug (AED) with multiple mechanisms of action and a chemical structure unrelated to other AEDs, which means it is unlikely to interact with other drugs.[2] Importantly, it has pharmacokinetic properties allowing for the clinical advantage of once-daily dosing after the titration phase.

Zonisamide was approved in Europe in 2005 as an adjunctive therapy in the treatment of partial seizures (with or without generalisation) in adults with epilepsy. In July 2012, the EMA issued Marketing Authorisation Approval to extend the use of zonisamide to include monotherapy for the treatment of partial seizures (with or without secondary generalisation) in adults with newly diagnosed epilepsy.

The 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.

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]

Zonisamide is available in 25mg, 50mg, and 100mg capsule strengths. 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]

About the CATZ study
The double-blind, randomised, multicentre, placebo-controlled study set out to assess the efficacy and safety/tolerability of adjunctive zonisamide in 207 paediatric patients (6-17 years) with partial-onset seizures who were on one or two anti-epileptic drugs. The study's primary endpoint was the proportion of responders (>/=50% seizure frequency reduction) after 12 weeks maintenance treatment. Safety/tolerability evaluation included assessment of treatment-emergent adverse events (TEAEs).[1]

About Epilepsy
Epilepsy is one of the most common neurological conditions in the world, affecting approximately eight in 1,000 people in Europe.[3] There are an estimated six million people living with epilepsy in Europe[4] and an estimated 50 million people worldwide[5], 10.5 million of which are children under the age of 15.[6]

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 the European market. 

In Europe, Eisai currently has three marketed treatments including:

• Zonegran® (zonisamide) as 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

About Eisai
Eisai is one of the world's leading R&D-based pharmaceutical companies and has defined its 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 recently expanded their UK Hatfield facility which now supports the company's growing European, Middle Eastern, African and Russian (EMEA) business.

Eisai concentrates its R&D activities in three key areas:

• Neuroscience, including: Alzheimer's disease, multiple sclerosis, neuropathic pain, epilepsy, depression
• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc and supportive cancer therapies; pain relief, nausea 
• Vascular/Immunological reaction including: acute coronary syndrome, atherothrombotic disease, rheumatoid arthritis, psoriasis, Crohn's disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 11,000 people worldwide. In Europe, Eisai undertakes sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic, Slovakia, the Netherlands, Belgium, Luxembourg, the Middle East and Russia.

For further information please visit our web site www.eisai.com

July 2012 / Zonegran-UK2445

References

[1] Rosati A, Pellacani P, Falchi M, Guerrini R.  Preliminary results from the CATZ Study: a phase III, double-blind, randomised, placebo-controlled trial to assess the efficacy and safety of adjunctive zonisamide in paediatric patients with partial-onset seizures. P870 Abstract#914  Presented at 29th International Epilepsy Congress, 28th August until 1st September, 2011, Rome
[2] Eisai Ltd. (2005). Zonegran Summary of Product Characteristics 
[3] Pugliatti M et al. Estimating the cost of epilepsy in Europe: A review with economic modeling. Epilepsia 2007: 48(12) 2224 – 2233.
[4] ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe 2010. Available from; http://www.ilae-epilepsy.org/Visitors/Documents/EUROReport160510.pdf (Accessed June 2011) 
[5] Epilepsy Society UK: http://www.epilepsysociety.org.uk/AboutEpilepsy/Whatisepilepsy/Epilepsy-didyouknow (Accessed June 2011)
[6] Forsgren L. Epilepsy in Children. 2nd Ed London. Arnold, 2004. 21–25