On September 10, 2020, Zogenix, Inc. (the “Company”) reported positive top-line results from its third Phase 3 study (Study 3) of FINTEPLA (fenfluramine) oral solution for the treatment of seizures associated with Dravet syndrome. The study corroborates the substantial impact of FINTEPLA on convulsive seizure reduction previously demonstrated in two earlier Phase 3 trials (Studies 1 and 2) in patients with this severe, rare and often debilitating form of infant-onset epilepsy. It also expands the countries where FINTEPLA has been evaluated to include Japan and Study 3 will be the pivotal study included in the Company’s planned submission of a new drug application (“J-NDA”) in that country, expected to occur in 2021.
Study 3 was a multi-national, randomized, double-blind, placebo-controlled, Phase 3 study enrolling 143 children and young adults with Dravet syndrome, whose seizures were not adequately controlled by existing anti-epileptic drugs. The median age of patients was 9 years (range, 2-18 years) and the average baseline convulsive seizure frequency across the study groups was approximately 63 seizures per month.
Following a six-week baseline observation period, patients were randomized to one of three treatment groups: FINTEPLA 0.7 mg/kg/day (26 mg maximum daily dose; n=49), FINTEPLA 0.2 mg/kg/day (n=46) or placebo (n=48), in which FINTEPLA or placebo was added to each patient’s current treatment regimen of anti-epileptic drugs. Patients were titrated to their target dose of FINTEPLA over two weeks and then remained at that fixed dose for 12 weeks.
The study met its primary objective in demonstrating that patients in the FINTEPLA 0.7 mg/kg/day group achieved a 64.8% greater reduction in mean monthly convulsive seizures compared to the placebo group (p<0.0001). The median percent reduction in monthly convulsive seizure frequency was 73.7% among FINTEPLA 0.7 mg/kg/day patients compared to 7.6% in placebo patients.
The same analyses comparing FINTEPLA at a lower dose of 0.2 mg/kg/day versus placebo was a key secondary objective and demonstrated that patients in the lower dose group achieved a 49.9% greater reduction in mean monthly convulsive seizures compared to placebo (p<0.0001). Collectively, these top-line data are highly consistent with the results of Study 1 in demonstrating a dose-response relationship for FINTEPLA in the treatment of convulsive seizures in Dravet syndrome.
Additional key secondary objectives of the study were to compare FINTEPLA 0.7 mg/kg/day and 0.2 mg/kg/day (independently) with placebo in terms of (1) the proportion of patients who achieved ³50% reductions in monthly convulsive seizures and (2) the median of the longest convulsive seizure-free interval. These results are shown in the following table. The proportion of patients who achieved ³75% seizure reductions, a secondary efficacy measure, is also presented.
| | | | | | |
| | | FINTEPLA
0.7 mg/kg/day
(N=48) | | FINTEPLA
0.2 mg/kg/day
(N=46) | | Placebo
(N=48) |
| | | |
Patients with ³50% reduction in monthly convulsive seizures | | 72.9%
(p<0.0001) | | 45.7%
(p<0.0010) | | 6.3% |
| | | |
Patients with ³75% reduction in monthly convulsive seizures | | 47.9%
(p=0.0001) | | 28.3%
(p=0.0047) | | 4.2% |
| | | |
Longest seizure-free interval (median) | | 43 days
(p<0.0001) | | 24 days
(p<0.0010) | | 13.3 days |
