Long-Term Safety and Efficacy of Once-Daily Zonegran® (zonisamide) Monotherapy Demonstrated in Extension of Pivotal Study

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Eisai Europe Limited

21 Oct, 2014, 23:01 GMT

HATFIELD, England, October 22, 2014 /PRNewswire/ --

Zonegran® (zonisamide) continues to be well-tolerated and efficacious when used as long-term monotherapy for the treatment of partial onset seizures in adults with newly diagnosed epilepsy, as demonstrated by a new publication in Epilepsia.[1] Zonisamide is 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 secondary generalisation, in adults, adolescents, and children aged six years and above.[2]  

The extension study assesses zonisamide versus carbamazepine monotherapy in patients from 72 sites in 17 countries in Europe, Asia, Australia, and South Africa, with over three-quarters exposed to over 24 months of treatment. No other currently available anti-epileptic drug (AED) has been studied in a double blind monotherapy setting over such a long duration of treatment.[1] Safety assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory parameters. Efficacy assessments included retention rate and the proportion of patients who remain seizure free for ≥24 months. Up to 81.6% of patients received the lowest target dose levels (zonisamide 300 mg/day; carbamazepine 600 mg/day).[1]

"Monotherapy is the optimal treatment approach for newly diagnosed epilepsy and zonisamide's proven long-term efficacy in this setting is demonstrated by this study. This treatment, which is easy to titrate and offers the advantage of once daily dosing, may improve adherence to treatment for people with epilepsy," commented Professor Michel Baulac, manuscript lead author and head of the clinical department at the Hôpital de la Pitié-Salpêtrière, Paris, France.

The international, multicenter, randomised, double-blind extension of the Phase III non-inferiority trial (Study 310)[3] shows that once-daily zonisamide monotherapy demonstrates favourable long-term safety and maintenance of efficacy in the treatment of partial onset seizures in adults with newly diagnosed epilepsy. Retention rates are similar between treatment groups at all time-points throughout the extension study. The proportion of patients who remain seizure free for ≥24 months is also similar for zonisamide (32.3%) and carbamazepine (35.2%). The incidence of treatment-related TEAEs is 26.3% for zonisamide compared with 19.6% for carbamazepine and the most frequently reported treatment-related TEAEs are decreased weight (5.1% vs. 0%), decreased appetite (3.6% vs. 0%), memory impairment (2.9% vs. 3.2%), and decreased hemoglobin (1.5% vs. 3.2%). Most TEAEs are of mild or moderate intensity.[1]

Zonisamide has multiple mechanisms of action and a chemical structure unrelated to any other AED.[2] It is one of only four AEDs with level A evidence of efficacy as initial monotherapy for adults with partial onset seizures, as defined in the latest International League Against Epilepsy (ILAE) guidelines.[5]

The continued development of zonisamide underscores Eisai's human health care (hhc) 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 market currently 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. Zonisamide is also indicated in Europe as adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults, adolescents and children aged six years and above.[1] 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.[1] Zonisamide is one of only four AEDs with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures.[4]Worldwide there has been an estimated 1,274,963 patient-years of exposure to zonisamide (from 31.03.1989 to 31.03.2013).[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.[1]

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

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.[6],[7]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  

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 management
  • 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, Iceland, Ireland, Austria, Denmark, Finland, Norway, Portugal, Czech Republic, Slovakia, the Netherlands, Belgium, Luxemburg, Russia and the Middle East.

For further information please visit our web site http://www.eisai.co.uk

References 

1. Baulac, M. et al. Long-term safety and efficacy of zonisamide versus carbamazepine monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy: Results of a phase III, randomized, double-blind study. Epilepsia 2014;55:1534-1543

2. Zonegran, Summary of Product Characteristics (updated October 2013): http://www.medicines.org.uk/emc/medicine/16240/ (accessed September 2014)

3. Baulac, M. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurology. 2012:11(7):579-588

4. Glauser T. et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013;54(3):551-63

5. Data on file: ZON2013-0003. Eisai Europe Ltd.

6. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf (Accessed July 2014)

7. 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: October 2014

Job code: Zonegran-UK2540