Adopting an Orphan Drug: Rufinamide for Lennox–Gastaut Syndrome

BACKGROUND: Lennox–Gastaut syndrome is a catastrophic pediatric epilepsy syndrome characterized by multiple types of treatment‐resistant seizures and high rates of seizure‐related injury. Current available treatments are inadequate, leaving patients with few treatment options and opportunities. METHODS: We conducted a double‐blind, randomized, placebo‐controlled trial of the antiepileptic drug rufinamide in patients with Lennox–Gastaut syndrome. Eligible patients between 4 and 30 years of age had multiple types of seizures (including tonic–atonic and atypical absence seizures) with a minimum of 90 seizures in the month before baseline and a recent history of a slow spike‐and‐wave pattern on EEG. RESULTS: After a 28‐day baseline period, 139 eligible patients were randomized; 138 patients received either rufinamide (n = 74) or placebo (n = 64) in addition to their other antiepileptic drugs. The median percentage reduction in total seizure frequency was greater in the rufinamide therapy group than in the placebo group (32.7% vs 11.7%, p = 0.0015). There was a difference ( p < 0.0001) in tonic–atonic (“drop attack”) seizure frequency with rufinamide (42.5% median percentage reduction) vs placebo (1.4% increase). The rufinamide group had a greater improvement in seizure severity ( p = 0.0041) and a higher 50% responder rate compared with placebo for total seizures ( p = 0.0045) and tonic–atonic seizures ( p = 0.002). The common adverse events (reported by 10% of patients receiving rufinamide) were somnolence (24.3% with rufinamide vs 12.5% with placebo) and vomiting (21.6% vs 6.3%). CONCLUSIONS: Rufinamide was an effective and well‐tolerated treatment for seizures associated with Lennox–Gastaut syndrome.