Fenfluramine treatment and seizure-free days in pediatric and adult patients with Lennox-Gastaut syndrome: A post hoc analysis.

The most common primary endpoint for assessing treatment efficacy in patients with Lennox-Gastaut syndrome (LGS) is change in frequency of seizures associated with a fall. Increased number of seizure-free days (SFDs) is more strongly associated with improved quality of life than seizure frequency reduction. Fenfluramine is approved for treatment of seizures associated with LGS in patients ≥2 years old. Data from a fenfluramine randomized controlled trial (RCT) in patients with LGS, and its open-label extension (OLE), were used to evaluate (1) mean change in percentage of SFDs (seizures associated with a fall, generalized tonic-clonic seizures, all countable [motor] seizures) from baseline overall and by baseline seizure quartile; and (2) relationships between percentage of SFDs and change in seizure frequency, and Clinical Global Impression-Improvement (CGI-I) scale scores. Fenfluramine treatment was associated with a greater increase in percentage of SFDs versus placebo (RCT; all seizure categories, p < .0001), and higher doses corresponded to greater percentages (OLE) consistently across baseline seizure quartiles. SFD correlations with seizure frequency were strong (ρ = -.776 to -.974); SFD correlations with CGI-I score were weak/modest (ρ = -.2494 to -.3203). Assessment of SFDs enhances the evaluation of treatment efficacy and may be clinically meaningful for patients with LGS and their families.