Weight loss drug a promising treatment for rare form of epilepsy, shows trial

A new potential treatment for a severe and rare form of epilepsy in young patients has emerged in the form of a drug called Fenfluramine, previously used as a weight loss agent. The drug has met all of its secondary endpoints in its second late-stage study and was shown to be effective in reducing convulsive seizures associated with the disease known as Dravet syndrome .

These are the findings of a second pivotal phase 3 study (Study 1504) of low-dose fenfluramine hydrochloride (ZX008, Zogenix) being investigated for the treatment of the Dravet syndrome.

The pharmaceutical company Zogenix, said, its lead drug ZX008, at a dose of 0.5 mg/kg/day (maximum, 20 mg/day), was superior to placebo when added to a stiripentol regimen.

"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, Necker Enfants Malades Hospital, France, and Principal Investigator of Study 1504, said in the company's news release.

"If approved, ZX008 has the potential to be a transformative treatment for the Dravet syndrome, a rare and serious form of epilepsy with few available treatment options," added Nabbout.

The double-blind, placebo-controlled, phase 3 study consisted of 87 patients aged 2 to 19 years (median age, 9 years) with Dravet syndrome from sites in the U.S., Europe, and Canada.

After a 6-week baseline observation period, the 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 around 25 seizures per month.

Key Findings of the Trial:

• Patients taking ZX008 achieved a 54.7% greater reduction in mean monthly convulsive seizures compared to placebo. The median reduction in monthly convulsive seizure frequency was 62.7% in the ZX008 group compared to 1.2% in placebo group.


• 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.


• 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 most common adverse events in the ZX008 group were decreased appetite, diarrhea, pyrexia, fatigue, and nasopharyngitis.


• Two patients in the ZX008 group had an adverse event leading to study discontinuation compared with one in the placebo group.

"Patients with the Dravet syndrome can often experience frequent, severe convulsive seizures that dramatically impact the 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."

Zogenix plans to submit applications for marketing approvals in the U.S. and Europe in the fourth quarter of 2018.