Long-term Fintepla reduces seizures in Dravet children, adults: Analysis
Patient outcomes tracked over 3.5 years of treatment in trial extension
Long-term use of the approved Dravet syndrome therapy Fintepla (fenfluramine) safely and consistently reduces seizure frequency in children and young adults with the genetic condition, according to the final analysis of an open-label extension of a Phase 3 clinical trial.
Dubbed ZX008-1503 (NCT02823145), the international long-term study tracked outcomes over 3.5 years of Fintepla treatment in Dravet patients, ages 2 to 35.
The results were described in a study titled “Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome,” which was published in the journal Epilepsia. The work was funded by Zogenix, the therapy’s developer, which has since been acquired by UCB.
“The publication of these new long-term findings, in which patients were exposed to Fintepla for up to 3.5 years and experienced durable and clinically meaningful reductions in seizure frequency, emphasizes the benefit of this treatment and our commitment to helping improve outcomes for patients with [Dravet syndrome] and other rare epilepsies,” Brad Chapman, head of U.S. epilepsy and rare syndromes at UCB, said in a company press release.
That release noted that treatment “was associated with a statistically significant and clinically meaningful sustained reduction in monthly convulsive seizure frequency.”
Fintepla approved for Dravet since 2020 in US, EU
Dravet syndrome is a rare type of epilepsy characterized by episodes of prolonged seizures that begin in the first year of life and that are hard to control with antiseizure medications.
Fintepla is an oral therapy approved since 2020 in both the U.S. and the European Union as an add-on to standard antiseizure medicines for Dravet patients, ages 2 and older. Its safety and efficacy were demonstrated in three placebo-controlled Phase 3 trials involving Dravet patients, aged 2-18: ZX008-1501 and ZX008-1502 (NCT02682927) and ZX008-1504 (NCT02926898).
The extension Phase 3 ZX008-1503 study, completed in 2023, was designed to assess the long-term safety and efficacy of Fintepla in Dravet patients. It involved 374 individuals who had either participated in one of the three Phase 3 trials or who had not been previously treated with Fintepla. To be eligible, participants had to be between the ages of 19 and 35.
At the start of the extension study, participants had a median of 14.7 convulsive seizures per month. Each received an oral solution of Fintepla, twice daily, at a dose of 0.2 mg/kg for the first month that was subsequently adjusted up to a mean of 0.43 mg/kg based on patient tolerability and efficacy.
Participants were required to receive at least one antiseizure medication throughout the study. Altogether, they were on a median of three such therapies, with the most common being valproate (77.3%) and clobazam (71.7%). Clobazam is sold as Onfi, with generics available.
Treatment with Fintepla spanned a median of 824 days, or about two years, and was given for as long as 1,280 days, or about 3.5 years.
Monthly seizures dropped by over 65% over 3.5 years
The results of the new analysis demonstrated that Fintepla was generally well tolerated, with a total of 11 patients (3%) discontinuing treatment due to an adverse event. Nearly all patients experienced at least one adverse event, most commonly fever (30%), the common cold (28%), reduced appetite (27%), and a drop in blood sugar levels (24%).
Three patients died due to sudden unexpected death in epilepsy, which was deemed unrelated to the therapy.
Efficacy data demonstrated a significant reduction, by 66.8%, in the monthly convulsive seizure frequency. Overall, 64.2% of the patients experienced a reduction in seizure frequency of at least half, and 21.3% a more than 90% drop, according to the company. Also, two patients were seizure-free throughout the study.
Patients experienced a 20% median increase in the days without convulsive seizures after the first month of treatment.
This analysis, showing that Fintepla was generally well tolerated over the long-term and increased seizure-free days, … provides additional evidence of the sustained tolerability and efficacy of this treatment.
Further analyses showed that the treatment was similarly effective in children younger than 6 and in older patients.
At the last visit, about 60% of patients were reported by caregivers and investigators to have much or very much improved, using the Clinical Global Impressions-Global Improvement scale.
Long-term Fintepla treatment was also associated with significant improvements in multiple subscales of the Quality of Life of Childhood Epilepsy score, including energy/fatigue, language, general health, and overall quality of life.
“This analysis, showing that Fintepla was generally well tolerated over the long-term and increased seizure-free days, builds on previous findings from … controlled trials in adults and children with [Dravet syndrome] and provides additional evidence of the sustained tolerability and efficacy of this treatment,” said Ingrid E. Scheffer, PhD, the study’s first author, and a professor and chair of pediatric neurology at the University of Melbourne, in Australia.
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