Cost-Utility Analysis of Add-on Stiripentol Vs Cannabidiol and Vs Fenfluramine in Dravet Syndrome in the USA

OBJECTIVES: Dravet syndrome (DS) is a rare, life-threatening developmental epileptic encephalopathy. Patients are often refractory to background anti-seizure medications (ASMs) and require ‘add-on’ therapy to improve seizures control. This study assessed the cost-utility of initiating stiripentol versus other licensed add-on therapies (cannabidiol, fenfluramine) or continued background ASM therapy in DS patients from age 2 years.

METHODS: A Markov model was developed with a three-monthly cycle and six health states: “Seizure Free” (100% reduction from baseline in monthly convulsive seizures frequency); “Profound Seizures Reduction” (75-<100%); “Clinically Meaningful Reduction” (50-<75%); “Not Adequately Controlled” (<50% reduction); “Maintenance Therapy” (following treatment discontinuation); and “Death”. Efficacy data were derived from an indirect treatment comparison of RCT data. DS-specific utility values and resource use were obtained from the literature. Drug costs were based on real-world dosing. Base case analyses adopted a 15-year time horizon and a US healthcare payer perspective in 2023. The Institute for Clinical and Economic Review willingness-to-pay threshold of $200,000/quality-adjusted life year (QALY) was used as a cost effectiveness benchmark.

RESULTS: Stiripentol generated the most QALYs of all therapies and had an incremental cost effectiveness ratio (ICER) of $103,923/QALY against cannabidiol and $89,110/QALY against continued background ASMs. Stiripentol economically dominated fenfluramine, generating more QALYs (+0.13) and being less costly (-$119,645). In addition, stiripentol was economically preferred or had an ICER below $200,000/QALY in a wide range of sensitivity and scenario analyses, including: initiation at age 6 months or in adults; longer or shorter time horizons; use of maximum licensed dosing; and adoption of a societal perspective

CONCLUSIONS: At a willingness-to-pay threshold of $200,000/QALY, stiripentol is a cost-effective add-on therapy compared with cannabidiol or fenfluramine and background ASMs. In addition to its robust clinical evidence, these health economic data further support the utilization of stiripentol as a first-line add-on therapy for treatment of seizures in DS.