Soticlestat in children with Dravet and Lennox-Gastaut

In the phase 2 ELEKTRA study, soticlestat treatment resulted in a statistically significant and clinically meaningful reduction in median convulsive seizure frequency in children with Dravet syndrome, and in a directional reduction in median drop seizure frequency in patients with Lennox-Gastaut syndrome. Soticlestat was generally well tolerated.

Dravet syndrome and Lennox-Gastaut syndrome are rare childhood epilepsies that are often resistant to current treatment with antiseizure medications. Soticlestat is a first-in-class, selective inhibitor of cholesterol 24-hydroxylase which catabolises cholesterol to 24S-hydroxycholesterol in the brain. The phase 2 ELEKTRA trial (NCT03650452) was a randomised, placebo-controlled, parallel-group study of soticlestat (≤600 mg/day weight-adjusted) in children (2–17 years) with Dravet syndrome with ≥3 convulsive seizures (n=51), or Lennox-Gastaut syndrome with ≥4 drop seizures per month (n=88) [1].

In the combined patient population, soticlestat-treated patients demonstrated a statistically significant median placebo-adjusted reduction in seizure frequency of 30.5% (P=0.0007) in the 12-week maintenance period. Over the full 20-week treatment period, patients receiving soticlestat demonstrated a median placebo-adjusted reduction of seizure frequency of 25.1% (P=0.0024). In the soticlestat group, there was a decrease of 36.5% in convulsive frequency during the maintenance period, while the placebo group experienced a median increase of 10.1%. This results in a significant placebo-adjusted median reduction in convulsive seizure frequency of 50% (P=0.0002). Patients with Lennox-Gastaut syndrome showed a median reduction in drop seizure frequency of 18.9% during the maintenance period, compared with a 2.2% median reduction in the placebo group. This resulted in a median reduction in a placebo-adjusted median reduction of 17.1% (P=0.1166). Results of the full treatment period were consistent with the changes in seizure frequency observed during the maintenance period.

The incidence of treatment-emergent adverse events was similar between the soticlestat and placebo groups (80.3% vs 74.3%). Serious adverse events were reported in 15.5% vs 18.6%. Lethargy and constipation were the most frequent treatment-emergent adverse events reported in soticlestat-treated patients with at least 5% difference from placebo. Safety findings were consistent with previous studies.

1. Hahn CD, et al. Efficacy, Safety and Tolerability of Soticlestat (TAK-935/OV935) as Adjunctive Therapy in Pediatric Patients with Dravet Syndrome and Lennox-Gastaut Syndrome (ELEKTRA). S1.005, AAN 2021 Virtual Congress, 17-22 April.

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Posted on 16 June, 2021