Levetiracetam (KEPPRA) is UCB Pharma's existing AED indicated as adjunctive therapy in the treatment of partial onset seizures in adult patients with epilepsy. Levetiracetam offers sustained efficacy in patients with refractory partial seizures, and its long-term tolerability is similar to that seen in the short-term placebo-controlled trials. Ucb 34714 is a new pyrrolidone derivative from the same chemical family as levetiracetam. As such it builds on all the existing properties of levetiracetam whilst potentially providing improved efficacy due to its distinctive pharmacological properties.
Estimates vary but it is estimated that between 40-50 million people world-wide suffer from epilepsy3. The mean prevalence for active epilepsy (i.e. continuing seizures with the need for treatment) is approximately 8.2 per 1,000 of the general population- although this may be higher in developing countries3.
New AED research and development
New AEDs with improved efficacy remain an unmet need for improving the quality of life of many epilepsy sufferers. Current AEDs efficacy remains limited with 30% of patients requiring add-on therapy5. Unfortunately the majority of these (25% of all epilepsy patients) will remain resistant to polytherapy and therefore suffer from refractory epilepsy5. In addition, treatment failure is often attributable to withdrawal due to adverse effects rather than lack of efficacy 5. Due to the effectiveness of levetiracetam in providing broad-spectrum seizure relief, recent research has focused on identifying new compounds with high affinity to levetiracetam's binding site (LBS), specific for the brain, in an effort to exploit and enhance the specific properties of this drug.
The discovery of ucb 34714 derives from in vitro screening of approximately 12,000 compounds for their affinity to LBS. The compound has been tested in various animal models of epilepsy against several parameters, including the ability to provide symptomatic relief from seizures, tolerability and disease modifying potential.
Symptomatic relief from seizures
The new data presented by Dr Henrik Klitgaard, CNS Research Director at UCB Pharma, demonstrate that ucb 34714 has a higher efficacy than levetiracetam in reducing epileptiform activity in vitro. This correlates with other comparative studies conducted in UCB Pharma in vivo in genetic and other chronic models of epilepsy showing that ucb 34714 is significantly more potent and efficacious in reducing seizure severity and duration in animal models mimicking both partial and generalised epilepsy.
Tolerability
When comparing the therapeutic index of ucb 34714 against referenced AEDs, it was found to have a wide safety margin in in vivo models of chronic epilepsy.
Disease modifying properties
The potential antiepileptogenic properties of ucb 34714 were assessed by examining its ability to inhibit kindling in mice. Kindling is a process of brain sensitisation to repeated stimulation with an initially subconvulsive electrical stimulation resulting in intensified seizure activity, culminating in generalised seizures. Inhibition of kindling development may therefore be considered to reflect antiepileptogenic properties.
Ucb 34714 was shown to have a potent and persistent ability to inhibit corneal kindling development. This supports that ucb 34714 may possess potential for improving epilepsy therapy.
Dr Thomas Beck, R&D Director at UCB Pharma, said, "The discovery of levetiracetam has lead the way to potential new therapies deriving from the same pharmacological family. At this very early stage, ucb 34714 appears to demonstrate even, broad utility across a number of neurological indications, which we will fully explore during clinical development"
Ucb 34714 which has been discovered and developed in UCB Pharma's research laboratories, is currently undergoing phase I clinical trials and will enter this year its phase II programme.
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.
For further information please contact:
Amanda Boswell
Ketchum London
Tel: + 44 207 611 3571
Fax: + 44 207 611 3850
Email: Amanda.boswell@ketchum.com
Brigitte Raoult
UCB Belgium
Tel: + 32 2 559 9359
Fax: + 32 2 559 9366
Email: Brigitte.raoult@ucb-group.com
References
1. Klitgaard H. AED discovery at UCB Pharma: Identification of ucb 34714. (21.03.2003) AED congress VII, Key Biscayne.
2. Ben Menachem et al. Evidence for sustained efficacy of levetiracetam as add-on epilepsy therapy. Epilepsy Research 2003, 53 (1-2): 57-64
3. WHO (2003) Epilepsy fact sheet number 165. Epilepsy: Aetiology, Epidemiology and Prognosis. www.who.int/inf-fs/en/fact165.html
4. The Epilepsy Foundation of Central Ohio (2003) Facts and Figures
5. Cockerell OC; Johnson AL; Sander JW; Shorvon SD, Prognosis of epilepsy: a review and further analysis of the first nine years of the British National General Practice Study of Epilepsy, a prospective population_based study. Epilepsia. 1997 Jan; 38(1): 31-46
*Notes to editors
- Keppra is currently indicated only as adjunctive treatment of partial onset seizures, with or without secondary generalisation, in adults with epilepsy..
- Significant clinical research with levetiracetam is ongoing, including paediatric, Primary Generalised Seizure and monotherapy trials.
- In April 2000 the USA became the first country to launch KEPPRA, 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.
- On March 6, 2003, the approval for marketing Keppra in Canada was obtained.
- 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 first have to prove themselves as adjunctive (add-on) therapy – usually in partial seizures – before applying for approval as monotherapy.