Stiripentol for the treatment of seizures in Dravet syndrome

ABSTRACT

Introduction: Dravet syndrome is an early childhood-onset epilepsy syndrome characterized by drug-resistant seizures, frequent episodes of status epilepticus, and the development of neurocognitive impairment. Seizure freedom in this condition is rare and there is a higher rate of sudden unexplained death in epilepsy patients (SUDEP) than other epilepsy syndromes. Stiripentol is a recently approved medication with an indication specifically for the treatment of seizures in children with Dravet syndrome.

Areas covered: Review of relevant literature including the current and emerging treatment of seizures in children with Dravet syndrome, with a focus on stiripentol. This includes a review of the literature regarding the mechanism of action, clinical efficacy, and safety/tolerability of stiripentol.

Expert opinion: Stiripentol has been available through expanded access programs resulting in a reduction of seizures and episodes of status epilepticus. With the Federal Drug Administration (FDA) approval, this treatment option will be more readily available to the Dravet syndrome population in the United States. The approval comes at a time of other treatment options also receiving approval (cannabidiol) and several products in ongoing studies (fenfluramine, TAK-935) providing additional treatment options and hope on the horizon for those impacted by this severe epilepsy syndrome.

KEYWORDS:

• Dravet syndrome
• stiripentol
• clobazam

Article highlights

• ● Dravet syndrome is a catastrophic, childhood-onset epilepsy syndrome with drug-resistant seizures and associated neurocognitive impairment.

• ● Stiripentol is a novel anti-seizure medication with a variety of effects, including enhanced GABA transmission and cytochrome P450 inhibition.

• ● In the treatment of seizures associated with Dravet syndrome, stiripentol demonstrates a responder rate between 55% and 70%.

Additional Information and Resources

• Dravet syndrome foundation (www.Dravetfoundation.org)

• Dravet Syndrome | Epilepsy Foundation (https://www.epilepsy.com/learn/types-epilepsy-syndromes/dravet-syndrome)

• Dravet syndrome – Genetic and Rare Diseases Information Center – NIH (https://rarediseases.info.nih.gov/diseases/10430/dravet-syndrome)

• Dravet Syndrome Information Page | National Institute of Neurological (https://www.ninds.nih.gov/Disorders/All../Dravet-Syndrome-Information-Page)

• www.dravet-syndrome.com

Declaration of interest

KG Knupp discloses research funding from the Pediatric Epilepsy Research Foundation, West pharmaceuticals and Zogenix Inc, consulting funding from Zogenix Inc (advisory board) and Greenwich pharmaceuticals (DSMB). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Biocodex provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.