OBJECTIVES: Dravet syndrome is a rare, catastrophic, highly refractory developmental and epileptic encephalopathy in children. Getting the best seizure control possible is the treatment’s goal. The objective of this study was to evaluate the cost implications of stiripentol, fenfluramine and cannabidiol, to achieve given level of seizure reduction or freedom, using NNT.

METHODS: Proportion of patients achieving reductions from baseline in monthly convulsive seizure frequency (MCSF) of >50% (clinically meaningful), >75% (profound) and 100% (seizure free) were derived from an indirect treatment comparison of RCTs data of stiripentol, fenfluramine and cannabidiol (on top of standard antiseizures medications) vs. placebo (standard of care). NNTs were calculated for pairwise comparisons versus placebo with the inverse of Absolute Risk Difference (RD). Annual drugs costs per patient were calculated based on wholesale acquisition costs, body weight of 30kg (based on the average patient weight [approx. 9 years old] in the RCTs) and approved dose of 50mg/kg/day for stiripentol, 0,7mg/kg/day for fenfluramine, 20mg/kg/day for cannabidiol and then multiplied by their respective NNTs to estimate the average annual cost per patient achieving a >50%, a >75% and 100% reduction in MCSF.

RESULTS: For convulsive seizures freedom, stiripentol (NNT=3) was statistically superior to both the fenfluramine (NNT=10) and cannabidiol (NNT=25). For the >50% and >75% reduction, stiripentol was numerically the most effective (NNT=2 for both) followed by fenfluramine (NNT=2; NNT=3), cannabidiol (NNT=6 ; NNT=10) This translates into annual costs for one adult patient to achieve 50%, 75% and 100% reduction of convulsive seizures of $130,448, $130,448, $195,673 for stiripentol, $224,956 ; $337,435, $1,124,784 for fenfluramine and $154,723, $257,872, $644,681 for cannabidiol respectively.

CONCLUSIONS: Stiripentol achieves the same or better clinical outcomes at a lower cost than cannabidiol or fenfluramine. Stiripentol should be considered as a cost-effective and highly efficacious treatment for Dravet syndrome patients.