Abstract Details

Title Efficacy, Safety, and Tolerability of Soticlestat (TAK-935/OV935) as Adjunctive Therapy in Pediatric Patients with Dravet Syndrome and Lennox-Gastaut Syndrome (ELEKTRA)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S1 - Epilepsy and Clinical Neurophysiology (EEG) 1 (2:40 PM-2:48 PM)

Poster/Presentation
Number 005

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.

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).

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.

Authors/Disclosures
Cecil D. Hahn, MD (The Hospital for Sick Children) PRESENTER	Dr. Hahn has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda Pharmaceuticals. Dr. Hahn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Hahn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Holberg EEG. Dr. Hahn has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Neurophysiology. Dr. Hahn has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for various legal firms. Dr. Hahn has received publishing royalties from a publication relating to health care. Dr. Hahn has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant with CADTH.
	No disclosure on file
Vicente Villanueva	No disclosure on file
	No disclosure on file
Dimitrios Arkilo, MD (Sage Therapeutics)	Dr. Arkilo has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Arkilo has received personal compensation for serving as an employee of Acadia Pharmaceuticals. Dr. Arkilo has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Dr. Arkilo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EcoR1. An immediate family member of Dr. Arkilo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. An immediate family member of Dr. Arkilo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medtronic. Dr. Arkilo has stock in Takeda Pharmaceuticals. Dr. Arkilo has stock in Acadia Pharmaceuticals. Dr. Arkilo has stock in Sage Therapeutics.
Peter B. Forgacs, MD	Dr. Forgacs has received personal compensation for serving as an employee of OVID Therapeutics Inc. Dr. Forgacs has received stock or an ownership interest from OVID Therapeutics Inc.
Mahnaz Asgharnejad, PharmD (Takeda Pharmaceuticals)	Mahnaz Asgharnejad, PharmD has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Mahnaz Asgharnejad, PharmD has stock in GlaxoSmithKline. Mahnaz Asgharnejad, PharmD has stock in Takeda Pharmaceuticals.
	No disclosure on file
Dennis J. Dlugos, MD	Dr. Dlugos has received research support from NIH. The institution of Dr. Dlugos has received research support from The Epilepsy Study Consortium.