Fintepla found to reduce seizures in children with hard-to-treat Dravet
New Phase 3 trial data further support therapy's use in pediatric patients
Fintepla (fenfluramine) significantly reduces seizure frequency in children and adolescents with Dravet syndrome who experience hard-to-treat seizures, according to new Phase 3 trial data.
These findings add to positive results from other Fintepla Phase 3 trials, further supporting the benefits of the approved add-on therapy for this pediatric patient population.
“The results of this … Phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of [Fintepla] in children with Dravet syndrome,” the researchers wrote, noting that “treatment resulted in a 65% greater reduction in convulsive seizure frequency than placebo.”
The team added that “patients treated with [Fintepla] also experienced significantly longer seizure-free intervals than patients in the placebo group.”
The study, “Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial,” was published in Epilepsia. It was funded by Zogenix, the company that developed Fintepla and has since been acquired by UCB.
New report focuses on findings from 143 children and adolescents
Fintepla was approved in the U.S. in 2020 as an add-on treatment to standard anti-seizure medications for preventing seizures in Dravet patients, ages 2 and older. Its use as an add-on therapy also is cleared in the European Union, and in Japan.
As part of its development program, two identical Phase 3 trials were launched: one conducted in North America (NCT02682927) and the other initially enrolling participants in Western Europe and Australia (NCT02826863). These two trials also were funded by Zogenix.
Both recruited Dravet patients, ages 2-18, who had seizures not completely controlled by their current medications, with four or more convulsive seizures per month in the three months prior to enrollment. Participants could not be using Diacomit (stiripentol) or Epidiolex as add-on therapies.
After a six-week baseline period to monitor seizure frequency and ensure trial eligibility, these pediatric patients were randomly assigned to receive either oral Fintepla (0.2 or 0.7 mg/kg) or a placebo, given daily.
Treatment was split into two equal doses per day and was slowly increased to the target dose over a two-week titration period. Maintenance treatment at this optimal dose then continued for 12 weeks, or about three months.
Due to slow enrollment, the two trials were combined prior to data analysis. A previous report concerning the first 119 enrolled participants showed that add-on Fintepla was superior to a placebo at reducing seizure frequency.
In the new publication, the scientists now reported findings from the remaining 143 patients enrolled in the two studies between February 2017 and July 2020. These included also patients from Japan who were enrolled in the second trial after the two studies were combined.
The patients’ mean age was 9.3 years, and all were receiving at least one anti-seizure medication, most commonly clobazam (sold under the brand names Onfi and Sympazan) and valproate. Average convulsive seizure frequencies prior to the treatment period ranged from 12.7 to 18 per month.
Overall, nine participants withdrew from the study early, for reasons including adverse events in three patients, patient/guardian decision in two, and lack of efficacy and death in one patient each.
Greater drop in seizure frequency seen with higher dose
As in the previous analysis of the first participants, the study met its main goal, with Fintepla resulting in a significant reduction in convulsive seizure frequency compared with a placebo. Specifically, those in the 0.7 mg/kg group demonstrated a 64.8% drop relative to a placebo, and those in the 0.2 mg/kg group experienced a 49.9% reduction.
Median seizure frequency declined by 73.7% in the high-dose group and 47% in the low-dose group from the baseline period to the treatment period. Both of these reductions were significantly greater than those observed in the placebo group, where a 7.6% drop in seizure frequency was observed.
Significantly more patients in either treatment group experienced at least a 25%, 50%, or 75% reduction in convulsive seizure frequency compared with those given a placebo.
Fintepla-treated patients also had longer seizure-free intervals, and six people in the high-dose group remained seizure free for the entire treatment period versus none in the other two groups.
Patients given 0.7 mg/kg of Fintepla daily also saw a significantly greater reduction in non-convulsive seizures relative to a placebo (by 77% vs. 21%).
Caregivers reported patients were much or very much improved with treatment in 62% of those in the high-dose group, 35% of those given the low dose, and 8% of those in the placebo group.
“The ratings provided by the investigators were virtually identical,” the researchers wrote.
[The findings] confirm the robust antiseizure response of [Fintepla] in the treatment of [Dravet syndrome].
Improvements in one of the two quality of life measures used in these studies were significantly greater with high-dose Fintepla than a placebo; changes in the other measure were comparable between groups.
Fintepla was generally well-tolerated, with most side effects being mild or moderate in severity, and consistent with the known safety profile of the medication. The most commonly side effects were diarrhea, fatigue, fever, low blood sugar, decreased appetite, sleepiness, and tremor. No cardiovascular issues were observed.
Altogether, the findings are in line with previous Phase 3 trial reports and “confirm the robust antiseizure response of [Fintepla] in the treatment of [Dravet syndrome],” the team wrote.
Many participants in these and other fenfluramine trials have since enrolled in an open-label extension study (NCT02823145), in which all received the therapy for three years. Data showed that benefits of Fintepla were sustained with long-term treatment.
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