Approved Dravet drug cuts seizures in diverse group of young patients
Data from 3 late-stage trials confirm effectiveness, support therapy's use
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Treatment with the approved Dravet syndrome drug Fintepla (fenfluramine) was more effective than a placebo at reducing seizure frequency and extending periods without seizures among a diverse group of children and adolescents with the rare disease, data from three late-stage clinical trials show.
The oral therapy, widely cleared for use by people with Dravet ages 2 and older, was also shown to improve overall functioning among patients, a pooled analysis of the trials found.
These benefits were seen across patient groups regardless of age or how many antiseizure medications individuals had previously tried. Positive results also were observed among participants whether or not they carried a disease-causing variant in SCN1A, the gene most commonly mutated in Dravet.
Fintepla’s safety profile was generally similar across all groups, and most common adverse events resolved by the end of the studies, the data also showed.
The findings — all from Phase 3 trials, which together enrolled more than 300 Dravet patients — support Fintepla as a treatment option across a broad range of people with this severe form of epilepsy, according to the researchers. Still, the team cautioned that some patient groups in the trials were small and that the analysis was conducted after the studies had been completed.
“Further studies with larger sample sizes (including adults) … are warranted,” the researchers wrote, adding that they’d also like to see studies designed in advance to assess how Fintepla works in different groups of Dravet patients.
Titled “Efficacy and safety of fenfluramine in Dravet syndrome: The impact of patient clinical characteristics,” the study was published in Epilepsia Open, the journal of the International League Against Epilepsy.
Dravet is a rare and severe type of epilepsy that typically begins in infancy and is marked by frequent seizures that are often difficult to control. Patients may also experience problems with movement, behavior, and cognitive development, and the disease is associated with an increased risk of premature death.
In more than 90% of cases, Dravet is caused by mutations in the SCN1A gene that disrupt the function of a sodium channel essential for proper electrical signaling in the brain. This can lead to bursts of uncontrolled nerve cell activity — the defining feature of a seizure. Mutations in other genes can also cause the disease.
Fintepla approval was based on the results of these 3 trials
Fintepla is approved in the U.S. and many other countries to treat seizures associated with Dravet. Its ability to reduce seizure frequency compared with a placebo was demonstrated in three Phase 3 trials: ZX008-1501 (NCT02682927), ZX008-1502 (NCT02826863), and ZX008-1504 (NCT02926898). Across these trials, the drug’s use also improved patients’ overall functioning and was generally well tolerated.
But whether certain patient characteristics influence how well people with Dravet respond to Fintepla has been less clear.
To investigate, researchers pooled data from 348 patients ages 2 to 18 who participated in the three trials. Among them, 216 received Fintepla at doses of 0.2, 0.4, or 0.7 mg/kg/day, and 132 received a placebo.
The team examined whether treatment response differed by age, previous treatment history, or SCN1A status. Patients were grouped as younger than 4 or 4 and older; by whether they had previously tried 1-3, 4-6, or seven or more antiseizure medications; and by whether they carried a disease-causing SCN1A variant.
Across these groups, Fintepla generally performed better than placebo, reducing monthly seizure frequency, extending periods without convulsive seizures, and improving overall functioning.
By age, Fintepla reduced monthly seizure frequency by 57.1% more than placebo in patients ages 4 and older, the data showed. A 42.1% greater reduction was seen in children younger than 4, but this difference did not reach statistical significance, the researchers noted.
Benefits were observed regardless of prior treatment history, the data showed. Compared with the placebo, Fintepla reduced monthly seizure frequency by an additional 46.5% in those who had tried 1-3 medications, 58.8% in those who had tried 4-6, and 55.7% in those who had tried seven or more.
Fintepla was similarly effective regardless of SCN1A status, reducing monthly seizure frequency by 53.8% more than placebo in patients with a disease-causing SCN1A variant and by 63.5% more in those without one.
Findings support therapy’s use earlier on
The benefits extended beyond reducing seizure frequency, the researchers noted. Fintepla significantly lengthened the longest stretch without a convulsive seizure in patients ages 4 and older, across all three previous-treatment groups, and in those with an SCN1A variant. Differences did not reach statistical significance in children younger than 4 or those without an SCN1A variant, the team noted.
Clinically meaningful improvements in overall functioning were also more common with Fintepla than the placebo across the groups examined, except among children younger than 4.
At the two lower Fintepla doses, meaningful improvements were more frequently reported among patients who had previously tried only one to three antiseizure medications than among those who had tried more. At the highest dose, improvement rates were similar regardless of previous treatment history, the data showed.
The researchers said these findings support considering Fintepla earlier in the course of Dravet treatment. However, the team cautioned that age and previous treatment history are closely related — younger patients have had less time to try different medications — making it difficult to determine whether earlier treatment itself leads to better outcomes.
Fintepla’s safety profile was similar across patient groups. Side effects were reported in 94% of Fintepla-treated patients and 81.8% of those given placebo, with decreased appetite, diarrhea, and fever among the most common. More than 80% of common side effects with Fintepla had resolved by the end of treatment.
“This pooled analysis further confirms the positive benefit/risk balance for [Fintepla] in patients with [Dravet],” the researchers concluded, though the team added that “larger sample sizes with additional … analyses are needed to support these findings.”
Nikki Youngberg
Our daughter was on Fintepla for almost 10 years and developed undesirable behavior - so undesirable it was inhibiting family and social functions and causing friction within the household. It definitely helped for the first 3-5 years, but the behavior started about 4-5 years into the trial, very discreetly, and slowly worsening until we cut it out completely. Now the behavior has become a habit and she has lost most of her communication abilities. So sad for us, but we are happy that it is helping so many others.