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

Abstract 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.