The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis.

Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles. Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL). Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA. A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence. Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of efficacy, safety and QoL when compared with available ASMs.

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Gil-Nagel reports consultancy or speakers’ honoraria from Eisai, UCB, GW Pharma, Esteve, Zogenix and Stoke Therapeutics, Angelini Pharma and Biocodex. He has been an investigator for GW pharma, Zogenix, UCB and Takeda. Dr Falip has received honoraria for advisory boards/consultancy and speaking fees from UCB Pharma, ESAI, Esteve, Bial, Zogenix, GW Pharmaceuticals and Livanova. Dr. Sánchez-Carpintero has received honoraria for advisory boards from GW Pharmaceuticals and Zogenix; she has been an investigator for GW Pharmaceuticals Zogenix and Takeda and has received speaking fees from Biocodex, GW Pharmaceuticals, and Zogenix. Dra Abad-Sazatornil has received speakers’ fees from Janssen, Sobi, Galapagos, Abbvie, Ipsen, Biogen. JAA is a president of Dravet Syndrome Foundation Spain (DSF). He and/or DSF have received grants and/or financial support from GW Pharma, Zogenix, Ovid Therapeutics, Encoded Therapeutics, Biocodex, Praxis, and StrideBio to help carry out some of the DSF’s foundational activities or provide consulting services. JAA honoraria has always been directly or indirectly donated to DSF. Dr Sancho-López has received honoraria for consultancy services from Angelini Pharma. Dr. Trillo-Mata has received honoraria for advisory boards from Arvelle Therapeutics, Zogenix International Ltd, GW Pharma Limited. No other potential conflicts of interest are reported.