Long-Term (2-Year) Safety and Efficacy of Adjunctive ZX008 (Fenfluramine Hydrochloride Oral Solution) for Dravet Syndrome: Interim Results of an Ongoing Open-Label Extension Study (4684)

Objective: To evaluate the long-term safety and efficacy of long-term fenfluramine (FFA) as an adjunctive antiepileptic drug for treating patients with Dravet syndrome. Background: A previous interim analysis demonstrated that 64.4% of patients achieved clinically meaningful (≥50%) reduction in monthly convulsive seizure frequency (MCSF) after a median 256 days of treatment. This current analysis examines the magnitude, consistency, and durability of effect of FFA up to 2 years. Design/Methods: Patients who completed phase 3 controlled studies enrolled in an open-label extension (OLE) study (NCT02823145). Patients started at 0.2 mg/kg/day FFA and were titrated to effect (maximum: 26 mg/day, or 17 mg/day with stiripentol). Seizure frequency was captured via hand-held e-diary. Effectiveness and safety were assessed at each office visit (monthly for the first 3 months, then every 3 months). Results: At time of analysis (2/15/2019), 330 patients were enrolled (mean±SD age: 9.0±4.6 years old [y/o]; 55% male; 28% Conclusions: Fenfluramine provided durable, clinically meaningful reduction in MCSF for up to 2 years of treatment and was generally well tolerated. FFA may represent an important new treatment option for patients with Dravet syndrome. Disclosure: Dr. Sullivan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dravet Syndrome Foundation, Epygenix (Consultant/Advisor); Epilepsy Study Consortium (Reviewer). Dr. Sullivan has received research support from Zogenix (with travel support). Dr. Stephane has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Arvelle, Biocodex, Biomarin, Eisai, GW Pharma, UCB Pharma, Vitaflo, Zogenix. Dr. Stephane has received personal compensation in an editorial capacity for Epilepsia (Associate Editor). Dr. Pringsheim has received research support from Zogenix. Dr. Knupp has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences (Data and Safety Monitoring Board). Dr. Knupp has received research support from Zogenix, West Pharmaceutical Services. Dr. Wirrell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biomarin, Mallinckrodt, Biocodex, Sunovion Pharma, and Dravet Syndrome Foundation. Dr. Wirrell has received research support from Zogenix and GW Pharma. Dr. Farfel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Zogenix. Dr. Farfel holds stock and/or stock options in Zogenix. Dr. Galer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Zogenix, Inc. Dr. Galer has received compensation for serving on the Board of Directors of Zogenix, Inc. Dr. Morrison has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Zogenix, Inc.. Dr. Morrison has received compensation for serving on the Board of Directors of Ownership interest: Zogenix, Inc.. Dr. Morrison holds stock and/or stock options in Ownership interest: Zogenix, Inc.. Dr. Lock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Zogenix (consulting). Dr. Gammaitoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Zogenix, Inc. Dr. Gammaitoni has received compensation for serving on the Board of Directors of Zogenix, Inc. Dr. Gammaitoni holds stock and/or stock options in Zogenix, Inc.Dr. Thiele has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GW pharma, Zogenix, West Therapeutics, Aquestive, Biocodex. Dr. Thiele has received research support from GW Pharma and Zogenix.