Eisai announced that the European Medicines Agency (EMA) has agreed to review its application to extend the use of Zonegran (zonisamide) as monotherapy in newly diagnosed patients with epilepsy with partial onset seizures with or without secondary generalization.

Zonisamide is an anti-epileptic drug with numerous second-generation mechanisms of action, whose chemical structure is unrelated to other anti-epileptic drugs and pharmacokinetic properties that allow treatment with a single daily dose. It is approved in Europe as adjunctive therapy in the treatment of partial onset seizures (with or without secondary generalization) in adults with epilepsy.

Epilepsy is one of the most common neurological disorders worldwide, affecting approximately 8 of every 1,000 people in Europe are estimated to live in Europe six million people with epilepsy and 50 million throughout the world.

The efficacy and safety of zonisamide as monotherapy has been demonstrated in a multi-centre double-blind trial comparing the efficacy and safety of zonisamide, once daily with carbamazepine (CBZ) (Tegretol  retard) controlled-release, twice daily as monotherapy in 583 adults with newly diagnosed partial epilepsy. The primary study endpoint was the proportion of patients seizure free at 6 months (depending on the population of the protocol). The study results showed that zonisamide was effective and well tolerated in patients newly diagnosed with epilepsy when used as monotherapy.

“As a pharmaceutical company based on research with a particular interest in epilepsy, we are not only determined to bring new and innovative therapies to market, but also to ensure that we maximize the clinical benefits of products that currently have permission,” explains Dr Bettina Bauer, Head of the Epilepsy Business Unit for the EU, Eisai Europe. “If approved as monotherapy, zonisamide offer patients newly diagnosed with epilepsy a new option that will help them improve control of their seizures.”

Zonisamide is licensed as adjunctive therapy in the treatment of partial onset seizures (with or without generalization) in adults with epilepsy. It has a broad spectrum anti-epileptic mechanisms of action and has no appreciable effect on steady-state plasma concentrations of other anti-epileptic drugs such as phenytoin, carbamazepine and valproate.

Zonisamide is available in capsules, with presentations of 25 mg, 50 mg and 100 mg. The recommended initial daily dose for adjuvant use is 50 mg in two divided doses. After a week, the dose may be increased to 100 mg a day. Thereafter, the dose can be increased at weekly intervals in increments of 100 mg.

In the monotherapy trial, dosing was once daily during the titration and the target dose. The initial dose was 100 mg once a day, overnight and was adjusted upward every two weeks until an initial target dose 300 mg / day of zonisamide or 600 mg / day carbamazepine. Zonisamide-treated subjects were more likely to suffer loss of appetite (7.8% vs 1.7%) and weight loss (6.8% vs. 0%). 13.2% of subjects lost = 10% of their body weight, 0.7% lost = 20%. There were more reports of psychiatric disorders (9.3% vs 4.7%), and some reports of dizziness (3.9% vs 7.7%) and rash (2.1% vs 4.3%) in subjects treated with zonisamide compared with those treated with carbamazepine. The most common adverse events were headache (ZNS: 10.3%, CBZ: 12.3%), decreased appetite (ZNS: 7.8%, CBZ 1.7%), somnolence (ZNS: 6, 0% CBZ: 7.7%), dizziness (ZNS: 3.9%; CBZ: 7.7%), weight loss (ZNS: 6.8%, CBZ: 0%), fatigue (ZNS: 4 , 6%, CBZ 4.0%), rash (ZNS: 2.1%, CBZ: 4.3%) and pyrexia (ZNS: 3.9%, CBZ 4.0%).

Today zonisamide in paediatric patients is investigated to evaluate the safety and efficacy in children and adolescents with partial onset seizures treated with one or two anti-epileptic drugs.

Epilepsy is one of the most common neurological disorders worldwide, affecting approximately 8 of every 1,000 people in Europe. An estimated six million people in Europe and about 50 million people around the worldwide are living with epilepsy. It is characterized by abnormal activation of impulses from nerve cells in the brain that cause crisis. Depending on the crisis may be limited to a body part or may be generalized when affecting the entire body.

Patients may also experience abnormal sensations, abnormal behaviour or impairment of consciousness. Epilepsy is a disorder of different causes, often unknown. However, anything that alters the normal activity of neurons, from illness to brain damage or tumours, can produce a crisis.

Eisai is committed to the development and commercialization of new treatments beneficial to improve the lives of people with epilepsy. The development of anti-epileptic drugs (AEDs) is one of the major strategic areas of Eisai in the European market.