New phase III data for ZX 008 for Dravet syndrome shows reduction in convulsive seizures

Top-line results from Study 1 were previously reported in September 2017. The new Study 1 results presented at AES showed the odds of achieving a clinically meaningful (at least 50%) or substantial (at least 75%) reduction in convulsive seizure frequency were 29 and 50 times higher, respectively, among patients treated with ZX 008 0.8 mg/kg/day than in patients treated with placebo.

The study also measured improvement on the Clinical Global Impression (CGI-C) rating. Fifty-five percent of patients treated with ZX 008 0.8 mg/kg/day were rated by parents/caregivers as very much improved or much improved in overall condition on the CGI-C compared to 10% of the placebo group (p=0.001) and 62.5% of patients treated with ZX 008 0.8 mg/kg/day were rated by investigators as very much improved or much improved in overall condition on the CGI-C compared to 10% of the placebo group (p=0.001).

A key secondary endpoint was the same analysis for a comparison of ZX 008 0.2 mg/kg/day and placebo. Patients taking ZX 008 0.2 mg/kg/day achieved a reduction in mean monthly convulsive seizures of 33.7% compared to placebo (p=0.019). ZX 008 0.8 mg/kg/day and ZX 008 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 (more than 10% in any treatment group) in Study 1 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 more than 10% 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. The updated Study 1 results, as well as additional data supporting the further investigation of ZX 008 in refractory epilepsies, were presented at the 71st American Epilepsy Society (AES) Annual Meeting.