Authors :
#N/A, PharmaWrite; Joseph E. Sullivan, University of California San Francisco; Orrin Devinsky, NYU Langone Medical Center; Bradley S. Galer, Zogenix, Inc.; Gail Farfel, Zogenix, Inc.; Douglas Haney, Independent Statistical Consultant; M. Scott Perry, Cook
Rationale:
Dravet syndrome (DS) is a rare, early-onset, treatment-resistant epileptic encephalopathy that negatively affects the health-related quality of life (QoL) of the patients, caregivers, and families. For example, the unpredictability and severity of seizures in DS patients leads to high levels of caregiver anxiety about leaving their child in others' care (Jensen 2017). In a recent Phase 3 clinical trial, 0.7 mg/kg/day fenfluramine (FFA) resulted in a 62.3% (95% CI: -47.7%, -72.8%; P<0.001) reduction in mean monthly convulsive seizure frequency compared to placebo over a 14-week treatment period, a common Phase 3 trial endpoint. However, reduction in seizure frequency does not adequately describe whether patients with residual seizures have moved meaningfully toward seizure freedom, in terms of fewer days with seizures and longer, reliable intervals of seizure freedom. Here, we present an alternative analysis of these results focusing on seizure-free intervals, the number of seizure-free days, and a time-to-event (TTE) analysis.