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FDA Approves New Drug to Treat Severe Form of Epilepsy

In November, the FDA approved rufinamide (Banzel) as an adjunctive treatment for seizures associated with a severe form of epilepsy called Lennox-Gastaut syndrome (LGS).

Rufinamide is a triazole derivative. Its exact mechanism of action is unknown, but it is thought to regulate the activity of sodium channels in the brain, which lead to seizures.

FDA approval was based on the results of a double-blind, placebo-controlled clinical trial led by Tracy Glauser, MD, director of the Comprehensive Epilepsy Program at the Cincinnati Children's Hospital Medical Center in Ohio. The trial, which was reported in 2008 in the May 20 Neurology, showed improved seizure control in 138 patients ages 4 to 30. All patients were being treated with one to three concomitant stable dose antiepileptic drugs.

Patients randomized to receive rufinamide were given a target dosage of 45 mg/kg/day on a twice-daily schedule for 12 weeks. Results showed that patients on rufinamide had a 32.7 percent median reduction and placebo-treated patients had an 11.7 percent median reduction in total seizure frequency. There was also a 42.5 percent median reduction in frequency of tonic-atonic or drop attack seizures — the primary cause of injury in LGS patients — in those on rufinamide compared with a 1.4 percent median increase for people taking placebo.

The drug, manufactured by Eisai Medical Research Inc. of Woodcliff Lake, NJ, was granted orphan drug status by the FDA because LGS affects fewer than 200,000 people in the United States. It will become available this month.

LGS typically begins before age 4 and can be caused by severe head injury, brain malformations, CNS infection, and inherited degenerative or metabolic conditions. No cause can be found in 30- to 35-percent of cases. LGS is characterized by frequent seizures mixed with brief, seizure-free periods and high rates of seizure-related injury. Most children with the syndrome have some developmental delays, behavioral disturbances, and impaired intellectual functioning.

“I believe rufinamide offers a real potential for improved therapy for a group of patients with Lennox-Gastaut syndrome,” said Orrin Devinsky, MD, professor of neurology, neurosurgery, and psychiatry at New York University Medical Center and director of the New York University Epilepsy Center. “I will definitely use rufinamide for these patients, especially since many are refractory to available medications and their seizure burden greatly impacts their quality of life.” He added that currently data for comparing rufinamide to other antiepileptic drugs for LGS are lacking but it may take a while for double blind comparative studies to emerge.

The most commonly observed adverse reactions seen in the trial were headache, dizziness, vomiting, drowsiness and fatigue, and nausea. Labeling will include a warning that antiepileptic drugs increase the risk of suicidal thoughts or behaviors in patients taking the drug, and patients should be monitored for suicidal thoughts or behavior and the emergence or worsening of depression.


• Glauser T, Kluger G, Sachdeo R, et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology 2008; 70:1950–1958.