Efficacy, Safety and Tolerability of Soticlestat (TAK-935/OV935) as Adjunctive Therapy in Pediatric Patients with Dravet Syndrome and Lennox-Gastaut Syndrome (ELEKTRA)
Cecil D. Hahn1, Yuwu Jiang2, Vincente Villanueva3, Marta Zolnowska4, Dimitrios Arkilo5, Peter B. Forgacs6, Mahnaz Asgharnejad5, Ying Yan6, Dennis Dlugos7
1The Hospital for Sick Children, 2Peking University First Hospital, 3Hospital Universitario y Politécnico La Fe, 4Plejady Medical Center, 5Takeda Pharmaceutical Company Limited, 6Ovid Therapeutics Inc, 7The Children’s Hospital of Philadelphia
Objective:

To characterize the efficacy and safety of soticlestat (TAK-935/OV935) in children with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in the ELEKTRA study (NCT03650452).

Background:

DS and LGS are rare childhood epilepsies that are often resistant to current treatment. Soticlestat has demonstrated efficacy in preclinical seizure models, including significant reductions in spontaneous seizures in a murine DS model.

 

Design/Methods:

ELEKTRA was a phase-2, multi-center, randomized, placebo-controlled, double-blind, parallel-group study of soticlestat (≤600 mg/day weight-adjusted) in children (2–17 years) with DS with ≥3 convulsive seizures, or LGS with ≥4 drop seizures, per month at baseline. Study endpoints included the effect of soticlestat on median seizure frequency change from baseline compared with placebo during the 20-week treatment period.  


Results:

The modified-intent-to-treat population included 139 participants who received ≥1 dose of study drug and had ≥1 efficacy assessment (DS, n=51; LGS, n=88). Overall, children treated with soticlestat (DS and LGS combined) showed a median placebo-adjusted seizure frequency reduction of 25.1% (p=0.0024) during the 20-week treatment period, with children in the DS cohort demonstrating a median placebo-adjusted seizure frequency reduction of 46.0% (p=0.0007), and children in the LGS cohort demonstrating a median placebo-adjusted seizure frequency reduction of 14.8% (p=0.1279). The incidence of treatment-emergent adverse events (TEAEs) was similar between the soticlestat and placebo groups (80.3% vs 74.3%). Serious adverse events were reported in 15.5% of participants receiving soticlestat and 18.6% of participants receiving placebo. No deaths were reported. The most frequent TEAEs reported in soticlestat-treated patients with at least 5% difference from placebo were lethargy and constipation.

Conclusions:

Soticlestat treatment resulted in a statistically significant reduction in median placebo-adjusted seizure frequency from baseline in children with DS, and in a directional reduction in seizure frequency in patients with LGS. Soticlestat appears to be generally well-tolerated.

Study funded by Takeda Pharmaceutical Company Limited and Ovid Therapeutics Inc.