Zogenix Announces Positive Top-Line Results from its Third Pivotal Phase 3 Clinical Trial (Study 3) of FINTEPLA® in Dravet Syndrome
- Results corroborate highly statistically significant convulsive seizure reductions seen in earlier multinational Phase 3 studies of FINTEPLA in Dravet syndrome
- FINTEPLA at 0.7 mg/kg/day achieved a 64.8% greater reduction in mean monthly convulsive seizures compared to placebo (p<0.0001) and FINTEPLA at a lower dose of 0.2 mg/kg/day achieved a 49.9% greater reduction in mean monthly convulsive seizures compared to placebo (p<0.0001)
- Positive study will support Japanese new drug application (J-NDA) submission, planned for 2021
“There remains a substantial unmet need in the Dravet treatment landscape globally and these compelling results corroborate the substantial levels of seizure control provided by FINTEPLA in Dravet syndrome that was also demonstrated in Studies 1 and 2,” said
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.
“Dravet syndrome is a rare, highly refractory form of childhood onset epilepsy marked by frequent and often prolonged seizures that are difficult to control with existing medications,” said
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 ≥50% 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 ≥75% seizure reductions, a secondary efficacy measure, is also presented.
|Patients with ≥50%
reduction in monthly
|Patients with ≥75%
reduction in monthly
FINTEPLA was generally well-tolerated in this study, with adverse events consistent with those observed in Study 1 and Study 2 and with the known safety profile of fenfluramine. The incidence of treatment-emergent adverse events was higher in the treatment groups as compared to the placebo group, with 91.7% (n=44) of patients in the 0.7 mg/kg/day group and 91.3% (n=42) of patients in the 0.2 mg/kg/day group experiencing at least one treatment-emergent adverse event compared to 83.3% (n=40) of patients in the placebo group. The incidence of serious adverse events was similar in all three groups with 6.3% (n=3) of patients in the 0.7 mg/kg/day group and 6.5% (n=3) of patients in the 0.2 mg/kg/day group experiencing at least one treatment-emergent serious adverse event compared to 4.2% (n=2) of patients in the placebo group, including one placebo patient who died due to SUDEP (sudden unexpected death in epilepsy). Prospective cardiac safety monitoring throughout the study showed that no study patients developed valvular heart disease or pulmonary arterial hypertension.
FINTEPLA was approved by the
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Source: Zogenix, Inc