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Eisai: Zonegran Well-Tolerated by Elderly Patients With Partial Epilepsy

Data Shows Zonegran® (Zonisamide) is Well-Tolerated by Elderly Patients With Partial Epilepsy

HATFIELD, England, July 16, 2013 /PRNewswire/ --

Pooled-analysis shows zonisamide as an effective partial epilepsy treatment for the elderly, as well as adults

Results from a pooled-analysis, published today in Acta Neurologica Scandinavica, show Zonegran® (zonisamide) is a well-tolerated treatment for partial seizures with or without secondary generalisation in the elderly population (65 years and above), when used as a monotherapy or adjunctive (add-on) therapy.

The safety results observed in the elderly patients (n=95) were similar to that seen in adults (n=1389), however, the incidence of treatment related and serious adverse events reported was lower, respectively 56% vs. 73%, 13% vs. 17%. Most treatment emergent adverse effects (TEAEs) were of mild-to-moderate intensity. The only serious or severe TEAEs reported by ≥2% elderly patients were 'convulsions' ([4%]). A decrease in weight of >10% in 11% of monotherapy-treated elderly patients was also noted. Zonisamide demonstrated a favourable safety/tolerability profile in elderly patients. No new or unexpected safety findings were identified' [1] A pooled analysis of safety data on the 95 elderly subjects has shown a relatively higher reporting frequency of peripheral oedema and pruritus compared to the adult population. Review of post-marketing data suggests that patients aged 65 years or older report a higher frequency than the general population of the following events: Stevens-Johnson syndrome (SJS) and Drug Induced Hypersensitivity syndrome (DIHS). However, this analysis could not assess these effects due to the small patient numbers.

Compared with the younger adult population, epilepsy in elderly patients differs in terms of aetiology, clinical presentation and prognosis.[ 2] The management of epilepsy in the elderly is complicated and challenging, particularly since levels of comorbidity and the need for associated medication are high.[ 3] Mortality among elderly people with epilepsy is particularly high, with 30 per cent of acute seizures resulting in status epilepticus, a life-threatening state where a seizure lasts 30 minutes or longer, or patients experience a cluster of shorter seizures for 30 minutes or more, with little or no recovery in between, carrying a 40 per cent risk of mortality.[ 4] , [ 5]

A quarter of newly diagnosed cases of epilepsy are in the elderly population.[6] In Europe, it's estimated 600,000 people aged 65 years and over have epilepsy, equivalent to 7 in 1,000. There are approximately 85,000 new cases being diagnosed each year,[7] and nearly one third of European citizens will be aged 65 or over by 2060.[8]

"The elderly analysis provides healthcare professionals and patients with the confidence and knowledge that zonisamide is a well-tolerated treatment approach for managing elderly people's epilepsy, which is also supported by its already strong heritage in the treatment of the condition," commented Eugen Trinka, Professor of Neurology, Paracelsus Medical University, Salzburg, Austria.

An effective monotherapy and add-on treatment, once-daily zonisamide is a second generation anti-epileptic drug (AED) with multiple mechanisms of action and a chemical structure which is unrelated to any other AEDs.[9] In the recent ILAE evidence review, Zonegran was classed as one of only 4 AEDs with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures.[10]

"Epilepsy affects a significant number of elderly people and there has been surprisingly little research into the condition in this patient population. These encouraging new data enhance our knowledge of Zonegran and show that it is a well-tolerated once-daily monotherapy or adjunctive treatment in wider patient groups, such as the elderly," commented Luigi Giorgi, Eisai Europe.

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 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.

About Zonegran (zonisamide)

Zonisamide is licensed in Europe as once-daily 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 a once-daily 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.[ 9 ]

Zonisamide is available in 25mg, 50mg, and 100mg capsule strengths. In the first two weeks, the recommended daily dose for monotherapy use is 100mg/day. In the third and fourth weeks the dose may be increased to 200 mg 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.[ 9 ]

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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.[11] , [12]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.

Zonegran in the elderly [ 1 ]

A study assessing the tolerability and safety of zonisamide in elderly patients with partial epilepsy which used a pooled analysis of data from 95 elderly patients over 65 years and compared to pooled data from 1389 adults (18-65 years).[13]  The assessments included treatment-emergent AEs, clinical laboratory tests and weight. Zonisamide was found to be well-tolerated by elderly patients when compared to adults and no new or unexpected safety findings were identified in the study.

Overall incidence of treatment-emergent adverse events (TEAEs) was similar in elderly versus adult patients (78/95 [82%] vs. 1165/1389 [84%]). Incidence was lower in elderly versus adult patients for severe TEAEs (11/95 [12%] vs. 299/1463 [20%]) and TEAEs leading to withdrawal (17/95 [18%] vs. 324/1463 [22%]). Most TEAEs were of mild-to-moderate intensity. TEAEs reported by ≥5% of patients in either cohort and more frequently by elderly versus adult patients were fatigue (11/95 [12%] vs. 135/1389 [10%]), nasopharyngitis (8/95 [8%] vs. 100/1389 [7%]), constipation (7/95 [7%] vs. 67/1389 [5%]), peripheral oedema (4/95 [4%] vs. 18/1389 [1%]), pruritus (6/95 [6%] vs. 29/1389 [2%]), and oropharyngeal pain (2/95 [2%] vs. 3/1389 [0.2%]).

The only serious or severe TEAEs reported by ≥2% elderly patients were 'convulsions' (4/95 [4%]) Three elderly patients died but only one death was considered treatment-related (circulatory collapse following pancreatitis). TEAEs leading to discontinuation of ≥2% of elderly patients were dizziness (4/95 [4%]), headache (2/95 [2%]), somnolence (2/95 [2%]) and confusional state (2/95 [2%]). For elderly patients, there were minimal clinically significant changes in clinical laboratory parameters, no reports of respiratory alkalosis or metabolic acidosis, and no significant weight changes.

A review of post-marketing data suggested that patients aged 65 years or older report a higher frequency than the general population of the following events: Stevens-Johnson syndrome (SJS) and Drug Induced Hypersensitivity syndrome (DIHS). However this analysis could not assess the effects of zonisamide on the incidence of certain adverse events of special interest, such as Stevens Johnson syndrome, pneumonia and bone disorders, which occur at frequencies too low to be investigated in such small patient numbers.[ 9 ]

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 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 recently expanded Knowledge Centre in Hatfield, UK, which now includes an additional high potency, global packaging capability, 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.

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1. Trinka E, Segieth J, Patten A, Giorgi L. Safety and Tolerability of zonisamide in elderly patients with epilepsy. Acta Neurologica         Scandinavica 2013.

2. Ramsay RE, Rowan AJ, Pryor FM. Special considerations in treating the elderly patient with epilepsy. Neurology 2004;62(Suppl 2):S24-9

3. Trinka E. Epilepsy: comorbidity in the elderly. Acta Neurol Scand Suppl 2003;180:33 ‒ 6.

4. DeLorenzo RJ, Hauser WA, Towne AR et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996;46:1029 ‒ 35.

5. Brodie MJ, Elder AT, Kwan P. Epilepsy in later life. Lancet Neurol 2009;8:1019 ‒ 30.

6. Stephen LJ. Epilepsy in elderly people. Lancet 2000;355:1441.6.

7. Forsgren L. The epidemiology of epilepsy in Europe - a symptomatic review. Eur J Neurol 2005;12:245. 53.

8. European Commission Ageing report: Europe needs to prepare for growing older (A cc essed 2012)

9. Eisai Ltd 2012. Zonegran Summary of Product Characteristics [ ]

10. Glauser T. et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. [Accessed April 2013]

11. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. [ Report 160510.pdf ] [A cc essed 10 April 2012].

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

13. Trinka E, Segieth J, Giorgi L. Tolerability and safety of zonisamide in elderly patients with partial epilepsy: results of a pooled analysis. Abstract ECE 2012 (p019)

Job code: Zonegran-UK2486

Date of preparation: July 2013

CONTACT: Media Enquiries: Eisai Europe Ltd, Cressida Robson / Charlotte Andrews, +44(0)7908 314 155/ +44(0)7947 231 513, , . Tonic Life Communications, Siobhan Reilly/Nicola Lilley, +44 (0) 207 798 9999/+44 (0) 207 798 9905, ,

Posted: July 2013