Results Presented for Pivotal Phase III Clinical Trial of Adjunctive Rufinamide in Children With Inadequately Controlled Lennox-Gastaut Syndrome

HATFIELD, England, December 5, 2016 /PRNewswire/ --

FOR EMEA MEDIA ONLY - NOT FOR SWISS/AUSTRIAN/US JOURNALISTS  

 Final data to be presented for the first time at American Epilepsy Society in Houston, Texas

Data presented today at the American Epilepsy Society (AES), Houston, Texas, show that adjunctive Inovelon^® (rufinamide) in children aged one to four years with inadequately controlled Lennox-Gastaut Syndrome (LGS) is well tolerated and cognitive development and behaviour is comparable to other adjunctive treatments.^[1]

Rufinamide is indicated in the European Union for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome in patients aged four years and older.^[2]

Study 303 (NCT01405053), a global, randomised, multicentre, two-year open-label study was conducted to evaluate the cognitive development and behavioural effects, safety, and pharmacokinetics of adjunctive rufinamide treatment in paediatric subjects aged one to four years with inadequately controlled Lennox-Gastaut Syndrome.^[3]

The primary endpoint of Study 303 was the change in Child Behaviour Checklist (CBCL) Total Problems Score from baseline to the end of the treatment period (106 weeks), which examines cognitive development and behavioural effects of subjects treated with rufinamide.^[1],[3] In Study 303, 25 children received rufinamide and 12 received another approved anti-epileptic drug as add-on to their existing regimen.^[1]

Using the Child Behaviour Checklist, the cognitive development and behaviour of children who received rufinamide was comparable to that of subjects who received another approvedanti-epileptic drug (LS mean difference [95% CI] +2.60 [-10.5,15.7]; p=0.6928).^[1]

The treatment-emergent adverse event (TEAE) incidence was similar between the rufinamide group (88.0%) and the any-other anti-epileptic drug group (83.3%), with most events considered mild or moderate. Vomiting (20%, n=5) and somnolence (16%, n=4) were the only treatment-related TEAEs reported in >2 children who received rufinamide.^[1]

"Lennox-Gastaut Syndome is a rare and severe form of epilepsy where children can have up to 100 seizures a day, causing multiple developmental issues. It is important to understand the impact of anti-epileptic drugs on the behavioural and cognitive development of these children. These data show adjunctive rufinamide has an impact on behavioural development comparable with other treatments," comments Alexis Arizmanoglou, Associate Professor of Neurology and Child Neurology, College de Medicine des Hopitaux de Paris.

Lennox-Gastaut Syndrome is a severe form of childhood-onset epilepsy that appears most often in children aged two to six. It is characterised by frequent and multiple seizure types, behavioural issues, mental retardation and resistance to medication or therapies.^[4] Although incidence is estimated to 0.1 in 100,000 people per year, the prevalence is high (5-10% of people with epilepsy), representing 1-2% of all childhood epilepsies.^[4]

"Eisai is committed to the ongoing development of rufinamide for this very rare and severe condition. Eisai seeks to improve the lives of patients and families through continued development of our products in epilepsy," comments Neil West, Vice President, Global Neurology Business Group, Eisai EMEA.

Notes to Editors  

About Inovelon^® (rufinamide)   

Rufinamide is a triazole derivative that is structurally unrelated to currently marketed antiepileptic drugs (AEDs).^[5],[6] It is believed to regulate the activity of sodium channels in the brain which carry excessive electrical charges.^[5] Rufinamide was approved for adjunctive therapy for seizures associated with Lennox-Gastaut Syndrome in Europe (under the brand name Inovelon) in 2007 in patients four years of age and older. Rufinamide is available as film-coated tablets containing 100mg, 200mg and 400mg rufinamide and as a 40mg/ml oral suspension.^[2]

About Epilepsy   

Epilepsy is one of the most common neurological conditions in the world, affecting approximately six million people in Europe, and an estimated 50 million people worldwide.^[7] 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 nature and 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) is indicated for use as a once-daily, adjunctive therapy for both primary generalised tonic-clonic seizures in idiopathic generalised epilepsy and for partial onset seizures, with or without secondary generalisation, in patients aged 12 years or older
• Inovelon^® (rufinamide) is indicated 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 secondary 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 countries.

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

References 

1. Arzimanoglou A et al. Safety and Cognitive Development Effects of Adjunctive Rufinamide in Pediatric Subjects With Inadequately Controlled Lennox-Gastaut Syndrome (LGS): Final Results From Study 303. Presented at American Epilepsy Society 2016

2. Inovelon® (rufinamide) SPC - Inovelon Tablets and Oral Suspension.  Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000660/WC500032938.pdf Accessed November 2016

3. Study of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs (NCT01405053). Available at: https://clinicaltrials.gov/ct2/show/record/NCT01405053 Accessed November 2016

4. Tyagi S, et al. Pharmacological management of Lennox-Gastaut Syndrome-a difficult-to-treat form of childhood-onset epilepsy: an overview. International Journal of Pharma and Bio Sciences. 2010:1(3).  Available at: http://www.ijpbs.net/issue-3/82.pdf . Accessed August 2016

5. Wier H et al. Rufinamide for Pediatric Patients with Lennox-Gastaut Syndrome. Pediatric Drugs 2011;13(2):97-106

6. Xu M et al. Pharmacokinetics and Tolerability of Rufinamide Following Single and Multiple Oral Doses and Effect of Food on Pharmacokinetics in Healthy Chinese Subjects. European Journal of Drug Metabolism and Pharmacokinetics 2016;41(5):541-548

7. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf (Accessed June 2016)

December 2016

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