KEPPRA for epilepsy

KEPPRA's place at the forefront of epilepsy management confirmed

New long-term data published today in an international medical journal - Epilepsy Research - show that KEPPRA (levetiracetam) offers sustained efficacy, as add-on, over the longer term - up to 54 months (4.5 years) - in reducing seizure frequency in adult patients with difficult to treat partial seizures. In addition, the data reveal that long-term treatment KEPPRA remains very well tolerated by the patients.

These data further demonstrate the favourable efficacy and safety profile of KEPPRA (levetiracetam), confirming its place at the forefront of the management of epilepsy. KEPPRA is currently indicated as adjunctive treatment of partial onset seizures, with or without secondary generalisation, in adults with epilepsy.

To our knowledge, this is the first and largest ever published study to collate data on patient retention and seizure freedom rates for adults with refractory epilepsy over a long-term (up to 54-month) treatment period. Data from 1,422 patients were analysed for changes in seizure frequency per week, seizure freedom and adverse events.

The lead investigator on this new study is Professor Elinor Ben-Menachem, from the Department of Clinical Neuroscience, Sahlgren University Hospital, Göteborg, Sweden. Commenting on the data, Professor Ben-Menachem said, "For the first time, long-term KEPPRA data from patients cohorts are available showing that treatment with KEPPRA gives effective, sustained antiepileptic benefits by reducing seizure frequency, as well as achieving the optimal treatment goal - seizure freedom. Our research shows that, with levetiracetam (Keppra), efficacy is sustained over long periods. This is good news for physicians, who can confidently choose KEPPRA to treat their patients in the long-term."

Significant reduction in seizure frequency

In this analysis, the median percentage reduction in seizure frequency from baseline did not decrease over time within each cohort (the sub-groups of patients) exposed to KEPPRA for varying periods of time. This suggests that tolerance with KEPPRA did not occur.

It is of importance to mention that patients included in the study suffered from a very refractory epilepsy, with a median seizure frequency per week of 2.17. The analysis revealed that overall, 38.6% and 20.1% of patients experienced a decrease in the numbers of seizures by at least 50% and 75% respectively. In addition, 4.6% of the 1,422 patients were completely seizure free from the first day of treatment until their last day, with the median duration of seizure freedom at 385 days. 11.7% of patients were seizure-free during the last 6 months of follow up, and 8.9% were seizure-free during the last 12 months. These data further confirm the strong efficacy of KEPPRA in the management of epilepsy.

Reduction in concomitant medication

The analysis also revealed that there was a tendency towards a reduction in the number of additional AEDs taken by patients; 14.4% of patients took a fewer number of AEDs at the end of the treatment compared to the start, and 5.5% of patients were only treated with KEPPRA at the end. The incidence of adverse events reported in this trial is very similar to the incidence described in previous clinical studies, confirming the safety and tolerability profile for KEPPRA.

"Seizure control, reduction and elimination are the key concerns for epileptologists and neurologists. Those new data show that levetiracetam could help doctors and patients achieve these goals. Levetiracetam represents a strong treatment option for many patients with epilepsy," commented Professor Ben-Menachem.

KEPPRA received approval by the FDA (U.S. Food and Drug Administration) in November 1999 and by the European Commission in September 2000. It is estimated that 50 million people world-wide have epilepsy [2].

KEPPRA spokesperson Dr Peter Verdru, UCB Global Medical Manager, CNS said, "These long-term seizure freedom results have convinced us to continue our commitment to investing in clinical research that may lead to the improvement of the quality of life of people with epilepsy".

KEPPRA was discovered and developed in UCB's research laboratories. UCB, with headquarters in Brussels (Belgium), is a pharmaceutical and chemical company which operates on a global scale. It is committed to pharmaceuticals, as well as to technically innovative products in surface specialities for flexible films and coating resins. It employs 10,000 people around the world. The pharmaceutical research of UCB includes the following fields : respiratory, including allergy and asthma, and neurology. UCB Pharma's principle products include Zyrtec(r), Xyzal(r) (anti-allergic), KEPPRA(r) (antiepileptic), Nootropil(r) (cerebral function regulator) and Atarax(r) (tranquilliser).

- KEPPRA is a registered trademark of the UCB Group

References:

1. Ben Menachem et al. Evidence for sustained efficacy of levetiracetam as add-on epilepsy therapy. Epilepsy Research 2003, 53 (1-2): 57-64

2. WHO Factsheet number 165: Epilepsy: Etiology, Epidemiology and Prognosis. http://www.who.int/inf-fs/en/fact165.html

Notes

- UCB continues to make a significant investment in future clinical research for KEPPRA(r), including paediatric, Primary Generalised Seizure and monotherapy trials.

- The KEPPRA Phase IV programme involves 2 trials; KEEPERTM in the USA and SKATETM in the rest of the world:

- KEEPER: was conducted in the USA in 1030 patients. Results were recently presented at the AES conference in Seattle in December 2002.

- The SKATE trial is ongoing involving more than 18 countries and 1,300 patients. Preliminary results of the SKATE trial in 730 patients will be presented by May 2003.

- In April 2000 the USA became the first country to launch KEPPRA(r), closely followed by Switzerland in May 2000.

- KEPPRA is now available in the following countries; Argentina, Austria, Belgium, Bulgaria, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong-Kong, Ireland, Italy, Luxembourg, Mexico, Netherlands, Norway, Poland, Singapore, South Africa, Spain, Sweden, Switzerland, UK and USA.

- A partial seizure (I) involves just part of the brain, and can be either 'simple' (Ia) when consciousness is not affected, 'complex' (Ib) when consciousness is affected or secondary generalised (Ic) when either a simple or complex seizure spreads to involve the whole brain.

- New antiepileptic agents such as KEPPRA(r) first have to prove themselves as adjunctive (add-on) therapy - usually in partial seizures - before applying for approval as monotherapy.

NEW STUDY1 CONFIRMS THE LOW PREVALENCE OF PSYCHIATRIC ADVERSE EVENTS (PAEs) WITH KEPPRA*

September 9th 2003 - Results from a new study published today in Neurology show that the prevalence of psychiatric adverse events (PAEs) with KEPPRA (levetiracetam) is low and not related to start dose or titration schedule1. The new data reaffirm that KEPPRA is well tolerated, and provide more information on individual patient susceptibility to PAEs, particularly suggesting that past psychiatric profile may be more important in predicting the features of psychiatric side effects than in predicting their occurrence. These results for KEPPRA compare favourably with data observed with other AEDs**3,4 .

Study results

In this new study, follow-up data from 517 KEPPRA treated patients at the National Hospital for Neurology and Neurosurgery, London, were evaluated.

Results show that 10.1% of patients developed PAEs during KEPPRA therapy, (classified as 2.5% affective disorder; 1.2% psychosis; 3.5% aggressive behaviour; 2.3% emotional liability and 0.6% other behavioural abnormalities)1, which is in line with what has been reported in placebo controlled clinical trials with KEPPRA4. There was found to be no relationship between these events and the starting dose of KEPPRA, or to its titration1 .

Occurrence of PAEs was not influenced by epilepsy diagnosis, seizure pattern and frequency, or disease duration. A significant association was demonstrated with previous psychiatric history and history of febrile convulsions or status epilepticus. However, previous psychiatric history was less predictive than a history of febrile convulsions or status epilepticus, suggesting that past psychiatric profile may be more important in predicting the features of the PAEs, than their occurrence.

These findings support previous clinical trial data, which have also identified a history of psychiatric problems as a risk factor for developing PAEs, while neither dose nor response to treatment (reduction of seizure frequency of = 50 %) had been identified as a prognostic factor2.

A recently published study by the same investigators, looking at PAEs in 431 patients treated with the AED topiramate, showed that PAEs occurred in 23.9% of topiramate treated patients3 (10.7% affective disorder, 3.7% psychotic disorder, 5.6% aggressive behaviour and 3.9% other behaviour abnormalities).

Professor Michael Trimble, Professor of Behavioural Neurology, Institute of Neurology, London, UK and lead investigator of the study, commented that "KEPPRA is such an interesting antiepileptic drug, because it renders many previously difficult to treat patients seizure free, and yet it has such a favourable side effect profile when it comes to behavioural problems. In the past, powerful seizure suppressing drugs have provoked more significant psychiatric adverse events."

KEPPRA was discovered and developed in UCB Pharma's research laboratories. UCB, with headquarters in Brussels (Belgium), is a pharmaceutical and chemical company, which operates on a global scale. It employs 12,000 people around the world. It is committed to pharmaceuticals, as well as to technically innovative products in surface specialities for flexible films and coating resins. The pharmaceutical research of UCB includes the following fields: respiratory, including allergy and asthma, and neurology. UCB Pharma's principle products include Zyrtec®, Xyzal® (anti-allergic), KEPPRA® (antiepileptic), Nootropil® (cerebral function regulator) and Atarax® (tranquilliser).

* Keppra is a registered trademark of the UCB Group. Please consult your national product information and regulatory status as they may differ from one country to the other

** These were gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin and zonisamide

References
1. Mula M. et al. Psychiatric adverse events during levetiracetam therapy. Neurology 2003; 61: 704
2. French J. et al. A systematic review of the safety profile of levetiracetam: a new antiepileptic drug.Epilepsy Research 2002; 47: 77-90.
3. Mula M. et al. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia 2003, 44(5): 659-663.
4. Cramer J.A. et al. A systematic review of the behavioural effects of levetiracetam in adults with epilepsy, cognitive disorders or an anxiety disorder during clinical trials. Epilepsy and Behavior 2003; 4(2): 124-132