Soticlestat Reduces Seizure Frequency in Dravet Syndrome, Study Shows

Both Dravet syndrome and Lennox-Gastaut syndrome (LGS) are characterized by frequent and often severe seizures. In many cases, those affected require multiple medications to manage their condition and prevent epileptic emergencies. Therefore, finding a therapy that could contribute to reduced seizures is extremely crucial for this community. According to Dravet Syndrome News, one such therapy may be on the horizon: soticlestat.

Data from the Phase 2 ELEKTRA study, published in Epilepsia, evaluated soticlestat for those with Dravet syndrome and LGS. 141 children, ages 2-17, enrolled. Over a 20-week period, patients received either soticlestat (up to 300mg 2x daily) or a placebo, administered via mouth or feeding tube. Findings from the study include:

  • At the start of the trial, patients experienced an average of 13 seizures each month. Soticlestat reduced seizure frequency by 50% in the first 12 weeks, and 45.95% over the entire course of the trial for those with Dravet syndrome. 
  • Those receiving soticlestat were also seen to improve in function and quality-of-life, according to physician and caregiver assessments. 
  • While soticlestat did reduce the frequency of seizures for those with LGS, this reduction was not considered to be statistically significant. 
  • Ultimately, soticlestat was relatively safe and well-tolerated. Some side effects did occur, with the most common being lethargy and constipation. Additionally, three participants discontinued due to more serious reactions.

Moving forward, the Phase 3 Skyline trial will further evaluate soticlestat for children and adolescents with Dravet syndrome.

Soticlestat: A Brief Overview

A 2021 news release from Takeda describes soticlestat as: 

a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H), with the potential to reduce seizure susceptibility and improve seizure control. Recent literature indicates that CH24H is involved in over-activation of the glutamatergic pathway through modulation of the NMDA channel and that increased expression of CH24H can disrupt the reuptake of glutamate by astrocytes, resulting in epileptogenesis and neurotoxicity.

Therefore, by inhibiting CH24H, soticlestat is designed to balance brain activity and reduce seizures. 

What is Dravet Syndrome? 

Dravet syndrome was first described in 1978 and later discovered to have a genetic basis in 2001. This rare genetic epileptic encephalopathy typically results from spontaneous SCN1A gene mutations, which affect neurons. Dravet syndrome is characterized by temperature-sensitive and treatment-resistant seizures which typically begin within the first year of life. The first seizures are usually febrile, meaning they occur with a fever. Later seizures may be triggered by hot weather or warm baths, though these may not be accompanied with a seizure. 

Other seizure forms include tonic-clonic seizures, hemiclonic seizures, myoclonic seizures, and partial seizures. Those with Dravet syndrome may also exhibit cognitive impairment, psychomotor delays, movement and balance issues, sleep difficulties, and behavioral disorders.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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