Zogenix Announces Updated Data from Pivotal Trial in Dravet Syndrome

Rare Daily Staff

Zogenix reported updated data from its first late-stage study of its experimental therapeutic ZX008 for the treatment of Dravet syndrome, a rare form of epilepsy.

Investigators presented the updated study results, as well as additional data supporting the further investigation of ZX008 in refractory epilepsies, at the 71^stAmerican Epilepsy Society Annual Meeting in Washington, D.C. 

The new results presented showed the odds of achieving a clinically meaningful (≥50%)were 29 percent higher,  or substantial (≥75%) reduction in convulsive seizure frequency 50 times higher,among patients treated with ZX008 0.8 mg/kg/day than in patients treated with placebo.

The study also measured improvement on the Clinical Global Impression (CGI-C) rating. Some 55 percent of patients treated with ZX008 were rated by parents/caregivers as very much improved or much improved in overall condition on the CGI-C compared to 10 percent of the placebo group and 62.5 percent of patients treated with ZX008 were rated by investigators as very much improved or much improved in overall condition on the CGI-C compared to 10 percent of the placebo group.

“Dravet syndrome is a rare form of intractable epilepsy for which a significant unmet medical need currently exists,” said Lieven Lagae, Director of the Childhood Epilepsy Program at the University of Leuven Hospitals, and Principal Investigator of study in Europe. “These new data demonstrate Dravet syndrome patients treated with ZX008 achieved a clinically meaningful reduction in seizure frequency. If approved, ZX008 could play an important role in changing the treatment paradigm for patients and their families whose lives have been greatly impacted by the lack of effective seizure control provided by current treatment options.”

As previously reported, the study met its primary objective of demonstrating that ZX008, at a dose of 0.8 mg/kg/day, is superior to placebo as adjunctive therapy in the treatment of Dravet syndrome in children and young adults based on change in the frequency of convulsive seizures between the 6-week baseline observation period and the 14-week treatment period. Patients taking ZX008 0.8 mg/kg/day achieved a 63.9 percent reduction in mean monthly convulsive seizures compared to placebo. The median percent reduction in monthly convulsive seizure frequency was 72.4 percent among ZX008 patients, compared to 17.4 percent in placebo patients.

A key secondary endpoint was the same analysis for a comparison of ZX008 0.2 mg/kg/day and placebo. Patients taking ZX008 0.2 mg/kg/day achieved a reduction in mean monthly convulsive seizures of 33.7 percent compared to placebo. ZX008 0.8 mg/kg/day and ZX008 0.2 mg/kg/day also demonstrated statistically significant improvements versus placebo in additional key secondary measures, including the proportion of patients with clinically meaningful reductions in seizure frequency and longest seizure-free interval.

The most common treatment emergent adverse events (>10% in any treatment group) in study include diarrhea, vomiting, fatigue, pyrexia, nasopharyngitis, upper respiratory tract infection, fall, weight decreased, decreased appetite, lethargy, seizure and somnolence. Prospective cardiac safety monitoring throughout the study demonstrated trace regurgitation on mitral or aortic valves were recorded on at least one echocardiogram in >10 percent of subjects among all three treatment groups, placebo included. There was no clinical or echocardiographic evidence of cardiac valvulopathy or pulmonary hypertension. No patient discontinued participation or required a change in monitoring in the study due to cardiac factors.

“Our confidence in the potential of ZX008 as an effective treatment for seizures associated with Dravet syndrome continues to strengthen with the new data showing that both caregivers and clinicians perceived patients’ overall condition to be very much or much improved following treatment with ZX008,” said Stephen Farr, president and CEO of Zogenix. “The overall data to date reinforce the potential of ZX008 to be an important new treatment for seizure control in children and young adults with Dravet syndrome.

The company expects to make top-line data from its second late stage trial of ZX008 in the second quarter of 2018.

ZX008 is designated as an orphan drug in both the United States and Europe, and has received Fast Track designation in the United States for the treatment of Dravet syndrome.

December 5, 2017