New Data for Zonegran® (Zonisamide), Fycompa® (Perampanel) and Zebinix® (Eslicarbazepine Acetate) to be Presented at the World Congress of Neurology

HATFIELD, England, September 21, 2013 /PRNewswire/ --

Eisai demonstrates commitment to continuous research in epilepsy

New data from three abstracts on Eisai's epilepsy portfolio are to be presented at this year's World Congress of Neurology (WCN) in Vienna. The abstracts include a long-term safety and efficacy clinical study of Zonegran^® (zonisamide) monotherapy,^[1] and two real-life safety and efficacy studies of Fycompa^® (perampanel)^[2] and Zebinix^® (eslicarbazepine acetate).^[3][*]

The first abstract to be presented at the WCN on Sunday 22 September shows that zonisamide monotherapy demonstrated favourable long-term safety and maintenance of efficacy in the study group (n=295), with no new or unexpected safety findings.^[1] This double-blind, extension study looked at the long-term safety and maintenance of efficacy of zonisamide versus carbamazepine monotherapy for partial seizures in adults with newly diagnosed epilepsy. The incidence of treatment-emergent adverse events (TEAEs) was similar for both zonisamide and carbamazepine (52.6% vs. 46.2%) as was the proportion of patients remaining seizure free for over 24 months (32.3% vs. 35.2%, intent to treat population).^[1]

Zonisamide is an anti-epileptic drug (AED) with multiple mechanisms of action and a structure which is chemically unrelated to any other AED.^[4] In July 2012, zonisamide received EMA approval as monotherapy in the treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy.^[4] Since March 2005, zonisamide has been used as an adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults.^[4]

Further data to be presented on Wednesday 25 September for eslicarbazepine acetate show nearly 20% (19.8%) of patients achieved seizure freedom, of which 65% had 0-1 previous AED exposures. Over 50% (52%) experienced a 50% or greater seizure frequency reduction.^[3] This study focused on the safety and efficacy of eslicarbazepine acetate in everyday clinical practice. Data from the study were gathered in a retrospective, multicentre audit across seven sites in the United Kingdom between 2009 and 2013 (n=202). Adverse events reported were consistent with eslicarbazepine acetate's known safety profile.^[3]

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[*]. Zebinix is under license from BIAL

Eslicarbazepine acetate is a third generation sodium channel blocker that selectively targets slow inactivated sodium channels. It is indicated as adjunctive therapy for adults with partial onset seizures, with or without secondary generalisation, and has an oral, once-daily dose regimen.^[5]

Additional data to be presented on Wednesday 25 September demonstrate that perampanel is well tolerated and leads to a significant improvement in seizure control for 22% of patients (75-100% reduction in seizure frequency).^[2] The study retrospectively examined data from 58 people who have received perampanel since 2009 and looks specifically at treatment response and adverse effects. The most common adverse effects reported include vertigo (31%), fatigue (14%) and nausea (7%). Adverse effects, in particular vertigo, can be avoided by taking perampanel immediately before bedtime or by dose reduction.^[2],[6]

Perampanel is the first and only licensed AED to selectively target AMPA receptors postsynaptically, which play an important role in the spread of epileptic seizures.^[6] Perampanel can be given once-daily and is indicated as adjunctive therapy for adolescents and adults with partial onset seizures, with or without secondary generalisation.^[6]

"We are delighted to present new data on our key epilepsy products at this year's WCN and are committed to conducting long-term and real-life studies such as these to increase our knowledge of these products and help people with epilepsy across Europe," commented Jenny Brown, Strategic Alliance & Marketing Director, Eisai EMEA. "The results demonstrate the strength and breadth of our epilepsy portfolio, which offers a range of once-daily treatment options for people with partial epilepsy, whether newly diagnosed or for those who require multiple anti-epileptic agents."

The continued development of its epilepsy portfolio 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 to address the unmet medical needs of people with epilepsy and their families. Eisai is proud to currently market 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. In addition, zonisamide is also indicated as adjunctive therapy in the treatment of partial seizures, with or without generalisation, in adults with epilepsy and has received European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) positive opinion for its use as a once-daily, adjunctive treatment of partial seizures, with or without secondary generalisation, in children aged six and above.^[7] 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.^[4] Zonisamide is one of only four AEDs with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures.^[8]

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.^[4]

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

About Fycompa (perampanel)

Perampanel is licensed in the European Union (EU) as an adjunctive treatment for people aged 12 years and older with partial onset seizures, with or without secondarily generalised seizures.^[5]

Perampanel is a highly selective, non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptor antagonist that has demonstrated seizure reduction in Phase II and III studies. AMPA receptors, widely present in almost all excitatory neurons, transmit signals stimulated by the excitatory neurotransmitter glutamate within the brain and are believed to play a role in central nervous system diseases characterised by excess neuroexcitatory signalling including epilepsy.^[5]

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

About Zebinix^® (eslicarbazepine acetate)

Eslicarbazepine acetate is a voltage-gated sodium channel blocker.^[9] It selectively targets the slow inactivated state of the sodium ion channel^[10],[11] (which have been implicated in the pathogenesis of epilepsy),^[12] preventing its return to the active state, and thereby reduces repetitive neuronal firing.^[9] Recent studies have also demonstrated that eslicarbazepine acetate effectively inhibits voltage-gated calcium channels, therefore enhancing its potential as an anti-epileptic agent.^[13] Further, eslicarbazepine acetate does not inhibit potassium efflux,^[14] which may reduce the potential for repetitive neuronal firings.^[15] The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study^[14] and three subsequent phase III randomised, placebo controlled studies in 1049 patients with refractory partial onset seizures.^{[16],[17],[18]}

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 eight in 1,000 people in Europe, and an estimated 50 million people worldwide.^[19],[20] 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 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. Baulac M, et al. A double-blind extension study to assess long-term safety/efficacy of zonisamide versus carbamazepine monotherapy for treatment of newly diagnosed partial epilepsy. WCN 2013 abstract 2015

2. Rohracher A, et al. Treatment response and adverse effects of perampanel add-on treatment 58 patients with refractory focal epilepsy. WCN 2013 abstract 235

3. Keogh S, et al. Safety and efficacy of eslicarbazepine acetate (Zebinix) in everyday clinical practice using a retrospective multicentre audit. WCN 2013 abstract 3219

4. Eisai Ltd 2013. Zonegran Summary of Product Characteristics [http://www.medicines.org.uk/emc/medicine/16240/SPC/Zonegran+25%2c+50%2c+100+mg+Hard+Capsules ](last updated February 2013)

5. Eisai Ltd 2013. Zebinix Summary of Product Characteristics [http://www.medicines.org.uk/emc/medicine/22376/SPC/Zebinix+800mg+tablets ] (last updated April 2013)

6. Eisai Ltd 2012. Fycompa Summary of Product Characteristics [http://www.medicines.org.uk/emc/medicine/26951/SPC/Fycompa+2mg%2c4mg%2c6mg%2c8mg%2c10mg%2c12mg+film-coated+tablets ](last updated November 2012)

7. Opinion of the Committee for Medicinal Products for Human use on a type II variation to the terms of the marketing authorsation for Zonegran, European Medicines Agency 2013

8. 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]

9. Almeida L, Soares-da-Silva P. Neurotherapeutics. 2007 Jan;4(1):88-96

10. Elger C et al. Epilepsia 2013; 54(8): 1453-1461.

11. Hebeisen S et al. Epilepsia 2012; 53 (Suppl. 5): 1-245.

12. Vilin YY and Ruben PC. Cell Biochem Biophys 2001; 35(2):171-190.

13. Brady K et al. Abstract presented at International Epilepsy Congress 2011 p858.

14. Elger et al. Epilepsia, 48(3):497-504, 2007

15. Soares-da-silva et al. Epilepsia. 52(Suppl. 6):23-263, 2011

16. Elger C, Halász P, Maia J et al. Epilepsia. 2009; 50(3):454-463

17. Ben-Menachem E, et al. Epilepsy Research 2010;89:278-285.

18. Gil-Nagel A, Lopes-Lima J, Maia J et al. Acta Neurol Scand 2009: 120: 281-28719. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [Accessed 18 July 2012].

19. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf [Accessed 18 July 2012].

20. Pugliatti M, et al. Epilepsia 2007: 48(12) 2224–2233.

Date of preparation: September 2013
Job code: Perampanel-UK2139