The US Food and Drug Administration (FDA) has approved Banzel (rufinamide) for the treatment of a severe form of epilepsy in adults and children aged four and over following review of the results of a trial that compared the drug with placebo as an adjunct therapy.

Banzel is marketed under license from Swiss-based Novartis Pharma AG by Eisai Corporation Ltd..

Eisai released a statement earlier this month stating that the drug had been approved for the adjunctive treatment of seizures linked to Lennox-Gastaut syndrome (LGS), one of the most severe forms of childhood epilepsy that accounts for 1 to 4 per cent of cases of epilepsy in children.

Approximately 300,000 children under the age of 14 in the U.S. have epilepsy and LGS accounts for 1 to 4 percent. Children are usually between 1 and 5 years old when symptoms start. About 3 to 7 per cent of LGS patients die within an average of under 10 years.

Symptoms include many types of seizures, the common ones being tonic or muscle stiffening, atonic such as loss of muscle tone or drop attacks, and absence or staring seizures. Drop attacks are seizures that cause the patient to lose consciousness and fall to the ground, they are a main cause of injury in LGS patients. Less common seizures include tonic-clonic (grand mal) and myoclonic (sudden muscle jerks).

LGS is difficult to treat and patients often take more than one antiepileptic drug (AED) to help control the seizures which, depending on their type and how often they occur, can delay development and cause behavioural problems.

Eisai’s statement said the company had received a “complete response letter” approving Banzel as:

“An adjunctive treatment for partial-onset seizures with and without secondary generalization in adults and adolescents 12 years of age and older.”

In a trial, LGS patients treated with Banzel as adjunctive therapy showed a median reduction in frequency of drop attacks of 42.5 per cent compared to a median increase of 1.4 per cent in patients treated with placebo. Lead investigator of the trial, Dr Tracy Glauser, Director, Comprehensive Epilepsy Program, Cincinnati Children’s Hospital Medical Center, Ohio, said:

“People living with LGS need more treatment options.”

The trial was a multicenter, double-blind, placebo controlled trial involving 138 male and female patients aged from 4 to 30 years who had been diagnosed with inadequately controlled seizures associated with LGS, who were already being treated with other AEDs and had had at least 90 seizures in the month leading up to the trial start date.

The trial started with a baseline of 4 week stable therapy phase where the patients just took the AEDs they were prescribed and then they were randomized to take either Banzel or placebo as well for a treatment phase of another 12 weeks. For the first one or two weeks of the treatment phase the dose was increased steadily to about 45 mg/kg/day. 88 per cent of the patients treated with Banzel reached this target dose.

The main results showed that:

  • Patients treated with Banzel had a 32.7 per cent median reduction in total seizure frequency per 28 days relative to baseline.

  • This compared to 11.7 per cent median reduction among the placebo patients.

  • Patients treated with Banzel had a 42.5 per cent median reduction in drop attack (tonic-atonic seizure) frequency per 28 days relative to baseline.

  • This compared to 1.4 per cent median increase among the placebo patients.

  • 53.4 per cent of the Banzel patients showed an improvement in seizure severity as measured by the Seizure Severity Rating from the Global Evaluation.

  • This compared to 30.6 per cent of the placebo patients.

  • There was a signficant difference between the two groups in favour of Banzel.

Glauser said that the trial showed Banzel was effective and generally well tolerated by children with LGS “whose seizures were previously uncontrolled on other multiple antiepileptic medications”.

Lonnel Coats, President and Chief Operating Officer of Eisai Corporation of North America said he was very pleased that the company “can offer this much needed new treatment option”.

Banzel is a triazole derivative that is thought to work by changing the way sodium channels in the brain carry the excessive electrical charges that cause seizures. It is not structurally related to any of the other currently marketed AEDs.

As with all AEDs there is an increased risk of suicidal thoughts and behaviour and patients should be watched closely for new or worsening symptoms of depression, suicidal thoughts or behaviour, or any uncharacteristic mood or behaviour changes.

Banzel has been linked to central nervous system side effects such as sleepiness, fatigue, problems with coordination (including ataxia), dizziness and gait disturbances.

Patients with Familial Short QT syndrome should not be treated with Banzel. Doctors should be careful about prescribing Banzel for patients taking drugs that shorten QT. Short QT is a inherited syndrome where the heart shows short Q to T intervals on an EKG scan (Q and T are types of waves).

The drug should be available for the treatment of LGS from January 2009.

Click here for more information on FDA approved drugs (Drugs@FDA).

Source: FDA, Eisai Corporation.

Written by: Catharine Paddock, PhD