Abstract Details

Title Efficacy, Safety and Tolerability of Soticlestat (TAK-935/OV935) as an Adjunctive Therapy in Patients with 15q Duplication Syndrome (Dup15q) or Cyclin-Dependent Kinase-Like 5 Deficiency Disorder (CDD) in a Signal-Finding Phase 2 Study (ARCADE)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) Epilepsy/Clinical Neurophysiology (EEG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 014

Background

Dup15q and CDD are rare, treatment-resistant epilepsies. Soticlestat is a highly selective first-in-class inhibitor of cholesterol 24-hydroxylase with efficacy supported by preclinical and clinical studies.

Objective

To characterize efficacy and safety of soticlestat (TAK-935/OV935) in patients with Dup15q or CDD in ARCADE (NCT03694275).

Design/Methods

Phase 2, open label signal-finding study. Inclusion criteria: age 2–55 years; 1–6 antiseizure medications; ≥3 motor seizures during 4-week baseline period. Treatment periods: 20-week total (8-week dose-optimization, 12-week maintenance). Maximum dose: soticlestat 600mg/day (weight-based dosing for patients <60Kg). Primary endpoint: median percent change from baseline in motor seizure frequency during maintenance period. Safety outcome: incidence of treatment-emergent adverse events (TEAEs).

Results

Twenty patients (dup15q, n=8; CDD, n=12) were enrolled in ARCADE (mean age, 10.7 years; 60% female). Primary outcome results showed median percent seizure frequency of +11.7% (Dup15q cohort) and -23.6% (CDD cohort) from baseline in motor seizure frequency during the maintenance period. The median change from baseline over the 20 weeks of treatment was +13.4% (Dup15q cohort) and –13.6% (CDD cohort). There were two early terminations during ARCADE. Nineteen ARCADE patients (95%) experienced TEAEs (mild, n=15 [75%]; moderate, n=10 (50%]; severe, n=3 [15%]). Serious TEAEs were reported by 3 patients (15%); none considered to be drug-related. The caregiver global impression of change scale demonstrated improvement in 11/12 (91.6%) CDD patients and 3/6 (50%) Dup15q patients. The clinician global impression of change scale demonstrated improvement in 8/12 (66.6%) CDD patients and 2/6 (33.3%) Dup15q patients. Long-term data are presented separately.

Conclusions

Results from the open-label ARCADE show a signal for seizure reduction in CDD but not in Dup15q patients, with positive trend in global impression scales for both syndromes. Overall, soticlestat was well tolerated in this study.

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

Authors/Disclosures
Scott T. Demarest, MD (University of Colorado Health Science Center, Child Neurology) PRESENTER	The institution of Dr. Demarest has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ovid. The institution of Dr. Demarest has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biomarin. The institution of Dr. Demarest has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tysha. The institution of Dr. Demarest has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Marinus. The institution of Dr. Demarest has received research support from NIH. The institution of Dr. Demarest has received research support from International Foundation for CDKL5 Research. Dr. Demarest has a non-compensated relationship as a SMAB with SLC6A1 Connect that is relevant to AAN interests or activities. Dr. Demarest has a non-compensated relationship as a SMAB with Ring 14 USA that is relevant to AAN interests or activities. Dr. Demarest has a non-compensated relationship as a SMAB with FamilieSCN2A that is relevant to AAN interests or activities.
Shafali Jeste, MD, FAAN (Children's Hospital of Los Angeles)	Dr. Jeste has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche Pharmaceuticals. Dr. Jeste has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharmaceuticals. Dr. Jeste has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN Continuum. The institution of Dr. Jeste has received research support from NIH. The institution of Dr. Jeste has received research support from DoD. The institution of Dr. Jeste has received research support from Dup15q Alliance.
Nitin Agarwal, MBBS	Dr. Agarwal has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai Inc.
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
Ronald L. Thibert, DO	Dr. Thibert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ovid Pharmaceuticals.