Raising the bar: Fenfluramine sets new treatment standards for Dravet syndrome

The clinical, economic, and humanistic burden of Dravet syndrome – A systematic literature review

“…In addition, the past few years have seen a rapidly changing treatment landscape with the approval of therapies such as fenfluramine, cannabidiol, and stiripentol, which have demonstrated efficacy in reducing the seizure burden in DS [20]. However, seizure freedom is rarely achieved and little impact is observed in motor function and neurodevelopmental manifestations of DS [20][21][22]. Previous portrayals of the clinical burden and evolution were largely based on expert opinion [12][13][14][15][16]23], and, to date, an evidence-based visualization of the clinical burden of DS by age across the contemporary literature is lacking.…”

Fenfluramine: A Review of Pharmacology, Clinical Efficacy, and Safety in Epilepsy

“…In the above mentioned three independent pivotal RCTs, the efficacy of FFA against convulsive seizures approximated the responder rate at the ≥75% level that was previously noted at the ≥50% level by other ASMs [ 58 ]. Furthermore, the number needed to treat (NNT) with FFA to achieve either ≥50 or ≥75% seizure reduction was 2–3, which is much more favorable than other ASMs used in Dravet syndrome (NNT of 4–6) or when ASMs were evaluated in treating other treatment-resistant epilepsies (NNT 8–20) [ 58 ]. Although these RCTs provided population-based metrics of FFA’s effectiveness, its effect on day-to-day seizure burden is also robust.…”

Complex epilepsy phenotype associated with chromosome 2q.24.2-2q24.3 deletion involving sodium channel gene cluster.

“…The mechanisms of action are under active investigation, however it is known that fenfluramine is a potent serotonin-releasing agent with activity at several 5-HT receptor subtypes. 7 Reports in zebrafish model of Dravet syndrome shows fenfluramine restores dendritic arborization, suggesting its potential for reduction in seizure activity. 7 In 2020, fenfluramine was approved for treatment of Dravet syndrome in the USA and Europe based on the results of 3 clinical trials that demonstrated reduction of the number monthly convulsive seizures by 54% to 65% compared to placebo.…”

“…7 Reports in zebrafish model of Dravet syndrome shows fenfluramine restores dendritic arborization, suggesting its potential for reduction in seizure activity. 7 In 2020, fenfluramine was approved for treatment of Dravet syndrome in the USA and Europe based on the results of 3 clinical trials that demonstrated reduction of the number monthly convulsive seizures by 54% to 65% compared to placebo. 7 This suggests that fenfluramine is an important new treatment option for patients with Dravet syndrome and potentially other developmental and epileptic encephalopathies.…”

“…7 In 2020, fenfluramine was approved for treatment of Dravet syndrome in the USA and Europe based on the results of 3 clinical trials that demonstrated reduction of the number monthly convulsive seizures by 54% to 65% compared to placebo. 7 This suggests that fenfluramine is an important new treatment option for patients with Dravet syndrome and potentially other developmental and epileptic encephalopathies. 7 However, there is little information about the potential efficacy of the combination of the ketogenic diet and fenfluramine in patients with complex epilepsy phenotypes involving larger deletions of chromosome 2.…”