Efficacy of Rufinamide as Adjunctive Treatment for Adults With Lennox-Gastaut Syndrome: Subgroup Analysis From a Phase III Trial (P2.056)

Objective: A post-hoc subgroup analysis of data from a Phase III trial was conducted to investigate the efficacy of rufinamide in adults with Lennox Gastaut Syndrome (LGS). Background: Rufinamide is a triazole derivative, structurally unrelated to other antiepileptic drugs, approved for adjunctive treatment of seizures associated with LGS in patients aged ≥1 years. LGS often persists into adulthood, or may have late-onset in adulthood.1 Management of LGS in adulthood is challenging; seizures are often intractable and most patients have moderate to severe cognitive impairment.1 Design/Methods: A randomized, double-blind, placebo-controlled trial was conducted in patients with LGS, aged 437 years, with history of multiple seizures types (including tonic-atonic and atypical absence seizures) and a minimum of 90 seizures prior to the 28-day Baseline period. During a 14-day Titration phase plus 70-day Maintenance period, patients received double-blind treatment with either rufinamide (titrated to ~45 mg/kg/day maximum) or placebo. Efficacy in adult patients (≥18 years) was assessed as median percentage change from baseline per 28 days of all seizures and tonic-atonic seizures during double-blind treatment. Results: Adults with LGS were randomized to adjunctive treatment with rufinamide (n=21; 15 Male, 6 Female) or placebo (n=10; 5M, 5F). Mean (standard deviation [SD]; range) age was 25.2 (4.7; 1835) and 29.3 (7.1; 1837) years in the rufinamide and placebo groups, respectively; mean (SD; range) time since LGS diagnosis was 18.5 (8.9; 033) and 25.5 (8.1; 834) years, respectively. Median change from baseline in seizure frequency was -31.5[percnt] for rufinamide versus +22.1[percnt] for placebo (p=0.008, Wilcoxon Rank-Sum test, unadjusted) for all seizures and -54.9[percnt] versus +21.7[percnt] (p=0.002), respectively, for tonic-atonic seizures. Conclusions: Rufinamide demonstrated favourable efficacy, compared with placebo, when used as adjunctive treatment for adults with LGS. Ref: 1Arzimanoglou et al. Lancet.2009;8(1):82-93. Support: Eisai Inc. Disclosure: Dr. Striano has received personal compensation for activities with Shire Pharma and Eisai Inc. Dr. McMurray has received personal compensation for activities with Eisai Ltd. as an employee.