|JAMA Neurology Publishes Phase 3 Study of Zogenix Investigational Drug FINTEPLA® in Dravet Syndrome Patients Taking Stiripentol-Containing Antiepileptic Drug Regimens|
|By: GlobenewsWire - 02 Dec 2019||Back to overview list
EMERYVILLE, Calif., Dec. 02, 2019 (GLOBE NEWSWIRE) -- Zogenix, Inc. (NASDAQ: ZGNX), a global pharmaceutical company developing rare disease therapies, announced today that JAMA Neurology has published the results of Zogenix’s Phase 3 study (Study 1504) of the investigational drug, FINTEPLA® (ZX008, fenfluramine oral solution), in Dravet syndrome patients whose antiepileptic drug treatment regimens included stiripentol but who were still experiencing a high number of convulsive seizures. Dravet syndrome is a rare, severe, and very difficult to treat infantile-onset epilepsy characterized by frequent, disabling seizures. The study demonstrated that adding FINTEPLA to these patients’ treatment regimens led to a significant and clinically meaningful (> 50%) reduction in monthly convulsive seizure frequency (MCSF).
“Because it is common for physicians to use stiripentol for their Dravet syndrome patients, it was important to evaluate the benefit and tolerability of adding FINTEPLA to a stiripentol-inclusive treatment regimen in those patients who were still experiencing frequent convulsive seizures,” said study author, Professor Rima Nabbout, M.D., Ph.D., Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Necker Enfants Malades Hospital, Paris, France, and Principal Investigator of Study 1504. “We found that adding FINTEPLA to a regimen containing stiripentol resulted in a significant and clinically meaningful reduction in monthly convulsive seizure frequency early and for the duration of the study period. Patients in the FINTEPLA arm also experienced longer seizure-free intervals, which is important as many were previously experiencing multiple seizures per week.”
Study 1504 was an international, double-blind, placebo-controlled Phase 3 study of 87 Dravet syndrome patients age 2-19 taking background anti-epileptic drug regimens that included stiripentol, randomized to placebo (n=44) or FINTEPLA 0.4 mg/kg/day (n=43)*. The study was conducted at 28 centers in Canada, France, Germany, the Netherlands, Spain, the United Kingdom and the United States. Eligible patients in the trial were experiencing seizures that were poorly controlled with their current anti-seizure medications consisting of stiripentol plus clobazam and/or valproic acid. After a 6-week period to establish baseline seizure frequency, patients were randomized to receive FINETPLA starting at a dose of 0.2 mg/kg/day, twice-daily with gradual blinded titration over a 3 week period to 0.4 mg/kg/d (maximum of 17 mg per day)* over 3 weeks. Patients maintained their regimen for an additional 12 weeks at a stable dose, then either continued treatment in an open-label extension study or discontinued treatment.
The study met its primary efficacy endpoint and all key secondary endpoints. Patients treated with FINTEPLA achieved a 54% greater reduction in mean MCSF than those receiving the placebo (95% CI, 35.6%-67.2%; p<0.001). Additionally, 54% of patients treated with FINTEPLA experienced a clinically meaningful (>50%) reduction in MCSF versus 5% with placebo (p<0.001). Profound seizure reduction (>75% reduction in MCSF) was experienced by 35% of FINTEPLA-treated patients compared to 2% with placebo (p=0.003). The median longest seizure-free interval was 22 days (3.0-105.0) with FINTEPLA and 13 days (1.0-40.0) with placebo (p=0.004).
In the study, FINTEPLA was generally well-tolerated and demonstrated a safety profile consistent with the findings of Zogenix’s first Phase 3 study of FINTEPLA in Dravet syndrome, called Study 1, as well as with findings from an analysis of the company’s ongoing open-label extension study (Study 1503). The most common adverse events in Study 1504 were decreased appetite (19 patients taking fenfluramine [44%] vs 5 taking placebo [11%]), fatigue (11 [26%] vs 2 [5%]), diarrhea (10 [23%] vs 3 [7%]), and pyrexia (11 [26%] vs 4 [9%]). Across all three studies, no patient exhibited clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension.
“Given the devastating and lifelong impacts associated with the frequent convulsive seizures experienced by Dravet syndrome patients, we are very much encouraged by the results of this study in patients still having many seizures on a stiripentol-containing medication regimen and by its publication in JAMA Neurology,” said Bradley S. Galer, M.D., Executive Vice President and Chief Medical Officer at Zogenix. “We hope that this and our other clinical study data will help clinicians better understand the potential that FINTEPLA, if approved, could have for patients needing additional novel treatment options.”
* Note: Zogenix originally presented Study 1504 data results in December 2018 at the 72nd American Epilepsy Society (AES) Annual Meeting. In that and other presentations, Zogenix expressed doses of FINTEPLA (ZX008, fenfluramine oral solution) as doses of the HCl salt, with an upper limit of 0.5 mg/kg/day and 20 mg maximum daily dose. Due to current regulatory guidelines, Zogenix has chosen to express study doses as the fenfluramine base-equivalent, with an upper limit dosing of 0.4 mg/kg/day and 17 mg maximum daily dose.
Copyright 2019 GlobenewsWire
|Back to overview list|