Zogenix Announces Positive Phase 3 Trial Results on the Efficacy and Safety of FINTEPLA® (ZX008) in Dravet Syndrome
Positive Data from Second Pivotal Phase 3 Trial (Study 1504) Consistent with Results of First Phase 3 Trial in Showing Highly Significant Convulsive Seizure Reduction for FINTEPLA versus Placebo
Clinically Meaningful Reduction in Convulsive Seizure Frequency for FINTEPLA Maintained Over Phase 3 Open-Label Extension Trial (Study 1503)
Data Presented During Late-Breaker Session at 72nd
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Study 1504: Positive Results from a Second Phase 3 Clinical Trial
Results from Study 1504 (poster 3.461) will be presented as a follow-up to top-line results that were released in
Clinically Meaningful Seizure Reduction
Children and young adults treated with FINTEPLA achieved a 54.0% greater reduction in mean monthly convulsive seizures compared to placebo (p<0.001). The median reduction in monthly convulsive seizure frequency was 63.1% in the FINTEPLA group compared to 1.1% in placebo patients.
The Study 1504 results showed the odds of achieving a clinically meaningful (≥50%) or substantial (≥75%) reduction in convulsive seizure frequency were 26 and 24 times higher, respectively, among patients treated with FINTEPLA 0.5 mg/kg/day than in patients treated with placebo. The study also demonstrated statistically significant differences in seizure-free intervals, with a median longest seizure-free interval of 22 days in patients treated with FINTEPLA 0.5 mg/kg/day vs.13 days for patients in the placebo group (p=0.004).
Safety Profile Consistent with Study 1; No Signal of Cardiovascular Toxicity
The incidence of serious adverse events was similar in both the treatment and placebo groups. The most common adverse events in the FINTEPLA group were decreased appetite (44%), pyrexia (26%), fatigue (26%), diarrhea (23%), and nasopharyngitis (16%).
There was no evidence of valvular heart disease (valvulopathy) or pulmonary hypertension in any patient at any time during the trial. These safety results are consistent with the findings of Study 1, as well as the now released interim analysis of long-term safety data from the OLE trial. Across all trials, no safety signal of any valvular heart disease has been identified to date.
Study 1503: Interim Analysis of Ongoing Open-Label Extension Trial Confirms Durability of Effectiveness and No Cardiac Toxicity for FINTEPLA in Dravet Syndrome
Data from Study 1503 will be presented in two posters, one that focuses on effectiveness and overall tolerability of FINTEPLA (poster 3.463) and a second on the long-term cardiovascular assessments and observations (poster 3.453).
A total of 232 patients in Study 1503 were included in the interim analysis of the ongoing OLE trial. The median duration of treatment with FINTEPLA was 256 days and the range was 58-634 days (equivalent to 161 patient-years of exposure to FINTEPLA). A total of 22 (9.5%) patients discontinued treatment: lack of efficacy (16), subject withdrawal (2), adverse event (1), Sudden Unexpected Death in Epilepsy (SUDEP) (1), physician decision (1), and withdrawal by caregiver (1). More than 90% of patients remained in the study.
Substantial Reduction in Seizure Frequency and Maintenance Over Time
The median percent reduction in monthly convulsive seizure frequency over the entire OLE treatment period was 66.8% (compared with baseline frequency established in the core Phase 3 studies). Over the same period, 64.4% of children and young adults demonstrated a >50% reduction in convulsive seizure frequency and 41.2% demonstrated a >75% reduction.
Reductions in convulsive seizure frequency was noted at the first timepoint measured, one month, and continued over the entire treatment period analyzed. Based on the most current assessment during the OLE treatment period, 66.1% of caregivers and 65.9% of investigators rated patients as “much improved” or “very much improved.”
“These long-term data show that the significant reductions in convulsive seizure frequency observed in children and young adults in the pivotal Phase 3 trials are maintained over extended periods of treatment with FINTEPLA,” said
Long-Term Safety of FINTEPLA Assessed; No Signal of Cardiovascular Toxicity
The occurrence of adverse events was consistent with the Phase 3 placebo-controlled studies. The most common adverse events occurring in more than 10% of children and young adults were pyrexia (22%), nasopharyngitis (20%), decreased appetite (16%), influenza (12%), diarrhea (11%), and upper respiratory tract infection (10%). A total of 13.4% of children lost >7% body weight at some point during the trial; in 42% of those children weight loss abated during the period covered by the interim analysis. Over the course of the OLE treatment period, one patient died from SUDEP that was deemed unrelated to FINTEPLA.
A total of 703 color doppler echocardiograms were performed to assess cardiovascular health at baseline, week 4 or 6, and then every 3 months during the OLE trial. No patient developed valvular heart disease (valvulopathy) or pulmonary arterial hypertension at any time after daily treatment with FINTEPLA.
“Long-term safety results are a critical aspect of the profile for any investigational medicine,” said study author Dr.
“Based on the strength and consistency of our clinical data for FINTEPLA in Dravet syndrome, we expect to conclude the submission of a New Drug Application (NDA) with the
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Source: Zogenix, Inc.