Therapeutic advances in Dravet syndrome: a targeted literature review

  • Introduction: Dravet syndrome (DS), a prototypic developmental and genetic epileptic encephalopathy (DEE), is characterized by an early onset of treatment-refractory seizures, together with impairments in motor control, behavior, and cognition. Even with multiple conventional anti-epileptic drugs, seizures remain poorly controlled, and there has been a considerable unmet need for effective and tolerable treatments. Areas covered: This targeted literature review aims to highlight recent changes to the therapeutic landscape for DS by summarizing the most up-to-date, evidence-based research, including pivotal data from the clinical development of stiripentol, cannabidiol, and fenfluramine, which are important milestones for DS treatment, together with the latest findings of other pharmacotherapies in development. In phase III, double-blind, placebo-controlled randomized controlled trials stiripentol, cannabidiol, and fenfluramine have shown clinically relevant reductions in convulsive seizure frequency, and are generally well tolerated. Stiripentol was associated with responder rates (greater than 50% reduction in convulsive seizure frequency) of 67%-71%, when added to valproic acid and clobazam; cannabidiol was associated with responder rates of 43%-49% (48%-63% in conjunction with clobazam), and fenfluramine of 54%-68% across studies. Therapies in development include soticlestat, ataluren, verapamil, and clemizole, with strategies to treat the underlying cause of DS, including gene therapy and antisense oligonucleotides beginning to emerge from preclinical studies. Expert opinion: Despite the challenges of drug development in rare diseases, this is an exciting time for the treatment of DS, with the promise of new efficacious and well-tolerated therapies, which may pave the way for treatment advances in other DEEs.
Author:Adam StrzelczykORCiDGND, Susanne Schubert-BastORCiDGND
Parent Title (English):Expert review of neurotherapeutics
Publisher:Taylor & Francis Group
Place of publication:Abingdon
Document Type:Article
Date of Publication (online):2020/08/16
Date of first Publication:2020/08/16
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2022/03/07
Tag:Cannabidiol; Dravet syndrome; epilepsy; epileptic encephalopathy; fenfluramine; rare diseases; stiripentol
Page Number:15
First Page:1065
Last Page:1079
A Strzelczyk reports personal fees and grants from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals, LivaNova, Marinus Pharmaceuticals, Medtronic, Sage Therapeutics, UCB Pharma, and Zogenix. S Schubert-Bast reports personal fees from Eisai, Desitin Pharma, GW Pharmaceuticals, LivaNova, UCB Pharma, and Zogenix. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed. Medical writing assistance was funded by Zogenix GmbH, Germany.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0