Fenfluramine, a drug that has previously been used as a weight-loss agent, continues to show promise as an antiseizure medication in young patients with Dravet syndrome.
Top-line results from a second pivotal phase 3 study (Study 1504) of low-dose fenfluramine hydrochloride (ZX008, Zogenix) show that the drug met the primary endpoint and all key secondary endpoints. ZX008, at a dose of 0.5 mg/kg/day (maximum, 20 mg/day), was superior to placebo when added to a stiripentol regimen, the company said.
The results are consistent with those reported in a prior phase 3 study of ZX008, as reported by Medscape Medical News.
"These impressive study results show the significant impact the addition of ZX008 made in reducing the burden of convulsive seizures for patients who are not adequately controlled using stiripentol, the standard of care for the treatment of Dravet syndrome in Europe," Rima Nabbout, MD, PhD, from Necker Enfants Malades Hospital, France, and principal Investigator of Study 1504, said in a company news release.
"If approved, ZX008 has the potential to be a transformative treatment for Dravet syndrome, a rare and serious form of epilepsy with few available treatment options," said Nabbout.
The double-blind, placebo-controlled, phase 3 study included 87 patients aged 2 to 19 years (median age, 9 years) with Dravet syndrome from sites in Europe, the United States, and Canada.
Following a 6-week baseline observation period, patients were randomly allocated to the addition of ZX008 or placebo to their stable background regimen of stiripentol plus other antiepileptic drugs. The mean baseline convulsive seizure frequency across all treatment groups was roughly 25 seizures per month.
Patients taking ZX008 achieved a 54.7% greater reduction in average monthly convulsive seizures compared with placebo (P < .001). The median reduction in monthly convulsive seizure frequency was 62.7% in the ZX008 group compared with 1.2% in the placebo group, the company said.
ZX008 also demonstrated statistically significant improvement vs placebo in both key secondary measures, including patients with clinically meaningful reductions (>50%) in seizure frequency and longest seizure-free interval.
ZX008 was generally well tolerated, with adverse events consistent with those observed in the prior study and the known safety profile of fenfluramine. The most common adverse events in the ZX008 group were decreased appetite, diarrhea, pyrexia, fatigue, and nasopharyngitis. No patient exhibited cardiac valvulopathy or pulmonary hypertension. Two patients in the ZX008 group had an adverse event leading to study discontinuation compared with one in the placebo group.
"Patients with Dravet syndrome can often experience frequent, severe convulsive seizures that dramatically impact quality of life for them and their families," Linda Laux, MD, from Ann & Robert H. Lurie Children's Hospital of Chicago, Illinois, said in the release. "For patients who continue to have significant seizures and need new treatments to reduce seizure frequency and improve quality of life, ZX008 may be an exciting and important new treatment option."
ZX008 is designated as an orphan drug in both the United States and Europe and has received breakthrough therapy designation in the United States for treatment of Dravet syndrome. The company plans to submit applications for regulatory approval in the United States and Europe in the fourth quarter of 2018.
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Cite this: Weight-Loss Drug May Cut Seizures in Rare Type of Epilepsy - Medscape - Jul 12, 2018.