UCB said results of a phase III trial demonstrating its antiepileptic drug (AED) in development Keppra XR (levetiracetam) extended-release tablets significantly reduced partial onset seizure frequency when administered as adjunctive therapy for adults with refractory epilepsy.

UCB is also the process of submitting a New Drug Application (NDA) for the use of Keppra XR in the adjunctive treatment of partial onset seizures in adults with epilepsy to the US Food and Drug Administration (FDA).

The phase III, multicenter, randomised, double-blind, placebo-controlled study evaluated efficacy, safety, and tolerability of extended-release levetiracetam tablets (2x500 mg) once-daily as adjunctive therapy in 158 refractory epilepsy patients, 12 to 70 years of age, with partial onset seizures.

"These data show that the once-daily, extended-release formulation of Keppra reduced the frequency of partial onset seizures in patients with uncontrolled epilepsy and was generally well tolerated," said Iris Loew-Friedrich, MD, PhD, global head of development, UCB.

The study met its primary endpoint for seizure reduction over placebo during the treatment period (p=0.038). The median per cent reduction of partial onset seizures in the extended-release levetiracetam group was 46.1 per cent compared to 33.4 per cent with placebo during the 12 week treatment period. Additionally, 24.0 per cent of patients randomised to the extended-release levetiracetam group had seizure frequency per week reduced by 75-100 per cent, compared with 11.4 per cent of patients in the placebo group. In the extended-release levetiracetam group 10.1 per cent of patients had 100 per cent reduction in partial onset seizures and 8.9 per cent were free from any type of seizure over the treatment period, compared to 2.5 per cent and 1.3 per cent in the placebo group, respectively.

The study also found that extended-release levetiracetam tablets were generally well tolerated. The most common reported adverse events that occurred more frequently in the extended-release levetiracetam group were somnolence, influenza, nausea, nasopharyngitis, irritability, and dizziness.

"In this study with a new formulation of Keppra about one in ten patients with refractory partial onset epilepsy achieved seizure freedom," said Dr. Jukka Peltola, Department of Neurology Tampere University Hospital, Finland. "There is an ongoing need for new antiepileptic drug options and extended release formulations offer the potential advantages of convenience and improved patient compliance."

Epilepsy is a chronic neurological disorder affecting 40 million people worldwide including 2.5 million people in the US. It is caused by abnormal, excessive electrical discharges of the nerve cells or neurons in the brain. Epilepsy is characterized by a tendency to have recurrent seizures and defined by two or more unprovoked seizures.

Keppra (levetiracetam) tablets were approved by the FDA in 1999 as adjunctive therapy in the treatment of partial onset seizures in adults with epilepsy. Since 1999, Keppra has received several supplemental indications as adjunctive therapy for epilepsy, making it one of the few treatments approved to treat seizure types that together account for more than 80 per cent of all seizures.

Keppra tablets and oral solution are indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy, myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy, and primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy. Keppra injection is indicated as adjunctive therapy in the treatment of myoclonic seizures in juvenile myoclonic epilepsy and partial onset seizures in adults with epilepsy. Keppra injection is an alternative for patients when oral administration is temporarily not feasible.

Keppra tablets and oral solution are associated with the occurrence of central nervous system adverse events including somnolence and fatigue, behavioural abnormalities, as well as haematological abnormalities. In adults experiencing partial onset seizures, Keppra is also associated with co-ordination difficulties. In adults experiencing partial onset seizures, the most common adverse events associated with Keppra in combination with other AEDs were somnolence, asthenia, infection and dizziness. In paediatric patients 4-16 years of age experiencing partial onset seizures, the most common adverse events associated with Keppra in combination with other AEDs were somnolence, accidental injury, hostility, nervousness and asthenia. In patients 12 years of age and older with juvenile myoclonic epilepsy, the most common adverse events associated with Keppra in combination with other AEDs were somnolence, neck pain, and pharyngitis. In patients 6 years of age and older with idiopathic generalized epilepsy, the most common adverse event associated with Keppra in combination with other AEDs was nasopharyngitis.

UCB, Brussels, Belgium is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialisation of innovative pharmaceutical and biotechnology products in the fields of central nervous system disorders, allergy/respiratory diseases, immune and inflammatory disorders and oncology. UCB achieved revenue of 3.5 billion euro in 2006.