(dailyRx News) Eisai Corporation of North America has announced that the U.S. Food and Drug Administration (FDA) approved Banzel (rufinamide) for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in children 4 years and older and adults.
One of the most severe forms of childhood epilepsy, LGS is characterized by multiple and frequent seizures. LGS accounts for 1 to 4 percent of all childhood epilepsy cases; approximately 300,000 children under the age of 14 in the U.S. have epilepsy.
Eisai received a complete response letter for Banzel as an adjunctive treatment for partial-onset seizures with and without secondary generalization in adults and adolescents 12 years of age and older. Banzel for LGS will be available to the public in January 2009.
A double-blind, placebo-controlled pivotal study of LGS patients treated with Banzel as adjunctive therapy showed a 42.5 percent median reduction in frequency of drop attacks, seizures that cause a person to lose consciousness and fall to the ground, compared with a 1.4 percent median increase for placebo-treated patients. Drop attacks are a primary cause of injury in LGS patients.
"People living with LGS need more treatment options," said Tracy Glauser, M.D., Director of the Comprehensive Epilepsy Program at Cincinnati Children's Hospital Medical Center and lead investigator in a clinical trial for Banzel. "What's exciting about this study is that Banzel was effective and generally well-tolerated in children with LGS whose seizures were previously uncontrolled on other multiple antiepileptic medications."
Children usually experience the onset of LGS between the ages of 1 and 5; approximately 3 to 7 percent of LGS patients die within a mean follow-up period of less than 10 years. The condition is difficult to treat, with patients often taking multiple antiepileptic drugs (AEDs) in attempts to control the seizures. The multiple types and frequency of seizures can lead to developmental delays, as well as behavioral disorders. Symptoms of LGS include a variety of seizure types, with tonic (muscle stiffening), atonic (loss of muscle tone/drop attacks) and absence (staring) seizures being the most common. Atonic seizures lead to the sudden falls seen in LGS patients known as "drop attacks," a primary cause of injury. Tonic-clonic (grand mal), myoclonic (sudden muscle jerks) and other seizure types can also occur.
Banzel is a triazole derivative that is structurally unrelated to currently marketed antiepileptic drugs (AEDs). It is believed to exert its effect by regulating the activity of sodium channels in the brain which carry excessive electrical charges that may cause seizures.
About the Banzel Clinical Study
The effectiveness of Banzel as adjunctive treatment for the seizures associated with LGS was established in a multicenter, double-blind, placebo-controlled, randomized, parallel-group study (n=138). Male and female patients (between ages 4 and 30) were included if they had a diagnosis of inadequately controlled seizures associated with LGS (including both atypical absence seizures and drop attacks) and were being treated with one to three concomitant stable-dose AEDs. Each patient must have had at least 90 seizures in the month prior to study entry.
After completing a 4-week baseline phase on stable therapy, patients were randomized to have Banzel or placebo added to their ongoing therapy during the 12-week double-blind phase. The double-blind phase consisted of two periods: the titration period (one to two weeks) and the maintenance period (10 weeks). During the titration period, the dose was increased to a target dosage of approximately 45 mg/kg/day (3200 mg in adults of >70 kg), given on a b.i.d. schedule. Dosage reductions were permitted during titration if problems in tolerability were encountered. Final doses at titration were to remain stable during the maintenance period. Target dosage was achieved in 88 percent of the Banzel-treated patients. The majority of these patients reached the target dose within seven days, with the remaining patients achieving the target dose within 14 days.
The primary efficacy variables were as follows:
- The percent change in total seizure frequency per 28 days
- The percent change in tonic-atonic (drop attacks) seizure frequency per 28 days
- Seizure severity from the Parent/Guardian Global Evaluation of the patient's condition
Results of the primary efficacy variable analyses were as follows:
- Banzel-treated patients had a 32.7 percent median reduction and placebo-treated patients had an 11.7 percent median reduction in total seizure frequency per 28 days in the double-blind phase relative to the baseline phase (p<0.002).
- Banzel-treated patients had a 42.5 percent median reduction and placebo-treated patients had a 1.4 percent median increase in tonic-atonic ("drop attacks") seizure frequency per 28 days in the double-blind phase relative to the baseline phase (p<0.0001).
- An improvement in seizure severity was observed in 53.4 percent of the Banzel-treated patients compared to 30.6 percent of the placebo-treated patients in the Seizure Severity Rating from the Global Evaluation of the patient's condition (documented by the parent/guardian). There was a significant difference between the two treatment groups in favor of Banzel (p<0.005).
Banzel is a triazole derivative that is structurally unrelated to currently marketed AEDs. It is believed to exert its effect by regulating the activity of sodium channels in the brain which carry excessive electrical charges that may cause seizures.
Important Safety Information
Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in patients taking these drugs. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior or any unusual changes in mood or behavior.
Use of Banzel has been associated with central nervous system-related adverse reactions, such as somnolence or fatigue, coordination abnormalities, dizziness, gait disturbances and ataxia.
Banzel is contraindicated in patients with familial short QT syndrome. These patients should not be treated with Banzel. Caution should be used when administering Banzel with other drugs that shorten the QT interval.
As with all AEDs, Banzel should be gradually withdrawn to minimize the risk of increased seizure frequency. Multi-organ hypersensitivity syndrome has been reported in association with Banzel therapy. In clinical trials, hypersensitivity reactions occurred mostly in the pediatric population and usually within four weeks of starting Banzel therapy. If this reaction is suspected, Banzel should be discontinued and alternative treatment started. All patients who develop a rash while taking Banzel must be closely supervised.
In all patients with epilepsy treated with Banzel in double-blind, adjunctive therapy studies, the most commonly observed adverse reactions were headache, dizziness, fatigue, somnolence and nausea.
For full prescribing information or more information about Banzel, go to http://www.eisai.com/product.asp?ID=268.