Treatment with Zogenix‘s Fintepla (ZX008) provides a sustained and meaningful reduction in convulsive seizure frequency in young children with Dravet syndrome, with similar clinical efficacy to that seen in older patient groups, according to results from a long-term open-label extension (OLE) study.
Fintepla’s use also holds the potential to improve patients’ quality of life and help to regulate their emotional, cognitive, and executive thinking abilities.
These latest findings were recently presented during the 48th Annual Meeting of the Child Neurology Society held in Charlotte, North Carolina.
In the scientific poster, “ZX008 (Fenfluramine HCl Oral Solution) Provides Long-Term, Clinically Meaningful Reduction of Convulsive Seizure Frequency in Young (<6 Years Old) Dravet Syndrome Subjects: Analysis From a Long-Term Open-Label Study,”researchers presented an analysis of results in Dravet patients who entered trials before age 6 and had rolled into the open-label extension trial.
The OLE study (NCT02823145) includes 158 patients, age 2 to 18, diagnosed with Dravet syndrome. Each had completed one of two previous Phase 3 clinical trials (NCT02682927 and NCT02826863) testing the safety and efficacy of Fintepla, given as an oral solution.
About 26.6%, or 42 children, were younger than 6 upon entry into the Phase 3 studies. All OLE patients were treated with up to a maximum total dose of 30 mg/day of oral Fintepla, and were clinically evaluated every three months for up to 156 weeks (about three years).
In patients who were also using stiripentol, Fintepla was given at a maximum total dose of 20 mg each day.
Fintepla effectively reduced the median monthly frequency of convulsive seizures in these young children by 75% compared to their frequency at the study’s start. Similar results were seen in the overall trial population (2-18 years of age), with a median reduction in seizure frequency of 64% upon treatment with Fintepla.
The safety profile was also found to be similar between younger and older OLE patients, with the most common adverse reactions reported being diarrhea, fever, inflammation of the nose and throat, and decreased appetite.
These preliminary long-term results support that treatment with Fintepla offers a way of achieving a “sustained, clinically meaningful reduction in convulsive seizure frequency” in patients with Dravet.
“Importantly, effective control of seizures in this young age group might be expected to mitigate the negative neurodevelopmental outcomes reported to be associated with treatment-refractory seizures,” the researchers wrote.
Additional analyses of data collected from one of the core Phase 3 trials was also presented in a poster titled “Relationships Between Self-Regulation and Quality of Life: Results From a Phase 3 Study of ZX008 (Fenfluramine HCl Oral Solution) in Children and Young Adults With Dravet Syndrome.”
These data further demonstrated that Fintepla treatment holds the potential to improve patients’ quality of life and helps to regulate emotional, cognitive, and executive skills.
Dravet patients ages 5 to 18 were randomized to either Fintepla at 0.8 or 0.2 mg/kg/day or placebo, and treated for 14 weeks.
To assess behavior, researchers asked the patients’ caregivers to respond to the Pediatric Quality of Life Inventory (PedsQL) and the Behavior Rating Inventory for Executive Function (BRIEF) questionnaires before and after the study concluded. Ratings were available from caregivers of 77 of 119 patients (mean patient age, 10.7 years).
A strong association was seen between higher doses of Fintepla and greater improvements in self-regulation and life quality. In particular, improvement in BRIEF2 scores of self-regulation was associated with improvement in PedsQL physical, social, school, psychosocial, and total scores.
“The apparent dose-response effect observed with regard to the number of significant associations between changes in BRIEF2 and PedsQL scores could suggest an important contribution of seizure control and/or an independent drug effect on self-regulation,” the researchers wrote.
Fintepla is a low-dose oral solution of fenfluramine hydrochloride being developed by Zogenix to treat epileptic seizures linked to Dravet syndrome. Its anti-epileptic properties are associated with the stimulation of serotonin release in the brain.
After an initial refusal by the U.S. Food and Drug Administration (FDA) to review a New Drug Application (NDA) for Fintepla — due to incomplete submission of early studies and an accuracy problem in one clinical dataset, Zogenix is now planning to resubmit a request for the therapy’s approval, possibly by the end of the year.