This morning, pharmaceutical company Zogenix (ZGNX 54.05, +7.75, +16.7%) reported positive top-line results from its second confirmatory Phase 3 study (Study 1504) for its investigational drug, ZX008 (low-dose fenfluramine hydrochloride), for the treatment of children and young adults with Dravet syndrome.
The study results, which are consistent with those reported in Study 1, Zogenix’s first pivotal Phase 3 study, successfully met the primary endpoint and all key secondary endpoints, demonstrating that ZX008, at a dose of 0.5 mg/kg/day (maximum 20 mg/day), is superior to placebo when added to a stiripentol regimen.
Specifically -- Patients taking ZX008 achieved a 54.7% greater reduction in mean monthly convulsive seizures compared to placebo (p<0.001). The median reduction in monthly convulsive seizure frequency was 62.7% in the ZX008 group compared to 1.2% in placebo patients. ZX008 also demonstrated statistically significant improvement versus placebo in both key secondary measures, including patients with clinically meaningful reductions (>50%) in seizure frequency and longest seizure-free interval.
Secondary endpoints, which assessed ZX008 compared to placebo in terms of the proportions of patients who achieved =50% reductions and =75% reductions in monthly convulsive seizures, as well as the median of the longest convulsive seizure-free interval, were also met.
Also, ZX008 was generally well-tolerated in this study with the adverse events consistent with those observed in Study 1 and the known safety profile of fenfluramine. No patient exhibited cardiac valvulopathy or pulmonary hypertension at any time in the study.
The double blind, placebo controlled, Phase 3 study (Study 1504) randomized 87 patients, with a median age of 9 years (range, 2-19 years), across sites in Europe, the United States, and Canada. Following a six-week baseline observation period, patients were assigned to one of two treatment groups in which ZX008 (n=43) or placebo (n=44) was added to their stable background regimen of stiripentol plus other antiepileptic drugs. The ZX008 dose of 0.5 mg/kg/day (20 mg maximum daily dose) in this study accounted for a drug-drug interaction between stiripentol and ZX008 and was designed to approximate the 0.8 mg/kg/day dose evaluated in Study 1 where stiripentol use was not permitted. The mean baseline convulsive seizure frequency across all treatment groups in Study 1504 was about 25 seizures per month. Patients were titrated to their target dose over three weeks and then remained at that fixed dose for 12 weeks.
The trial data comes a few weeks after GW Pharma’s (GWPH 147.30, +2.45, +1.7%) EPIDIOLEX (cannabidiol) oral solution was granted FDA approval for the treatment of seizures associated with Lennox-Gastaut Syndrome and Dravet Syndrome. As part of that approval process, EPIDIOLEX must be rescheduled from its current Schedule I before it can be made available to patients. EPIDIOLEX is expected to be available to appropriate patients by Fall 2018.
Zogenix plans U.S. and EU regulatory submissions for the fourth quarter of 2018.