On December 3, 2018, Zogenix, Inc. (the “Company”) reported that late-breaking data will be presented on the use of its investigational drug, FINTEPLA (ZX008;low-dose fenfluramine), in children and young adults with Dravet syndrome. These three presentations will include data from the second pivotal Phase 3 trial (Study 1504), and long-term efficacy and safety data from a formal interim analysis of the ongoing open-label extension (“OLE”) trial (Study 1503). Apost-hoc exploration of the clinical meaningfulness of seizure control from the first pivotal Phase 3 trial (Study 1) will also be presented. The data will be presented at the 72nd American Epilepsy Society Annual Meeting in New Orleans.
Study 1504: Positive Results from a Second Phase 3 Clinical Trial
Results from Study 1504 will be presented as afollow-up to topline results that were released in July 2018. Patients (n=87) were taking a background anti-epileptic drug (“AED”) medication regimen that included stiripentol and were randomized to placebo (n=44) or FINTEPLA 0.5 mg/kg/day (n=43). Consistent with Study 1, Study 1504 met the primary endpoint and all key secondary endpoints. Results demonstrated the statistically significant efficacy of FINTEPLA when added to a stiripentol regimen in children and young adults with Dravet syndrome.
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 (³50%) or substantial (³75%) 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 inseizure-free intervals, with a median longestseizure-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).
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
Data from Study 1503 will be presented in two posters, one which focuses on effectiveness and overall tolerability of FINTEPLA and a second on the long-term cardiovascular assessments and observations.
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 range58-634 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.
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.
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