Concomitant Drug Load Reduction During Adjunctive Cenobamate Therapy: Post-hoc Analysis of a Phase 3, Open-Label Study (P11-1.006)

Abstract

<h3>Objective:</h3> Changes in concomitant antiseizure medication (ASM) drug load after adding cenobamate were evaluated post-hoc in a subset of the open-label, phase 3 safety study. <h3>Background:</h3> Many patients with epilepsy require adjunctive therapy, which can increase their ASM drug load. <h3>Design/Methods:</h3> Patients 18–70 years old with uncontrolled focal seizures taking stable doses of 1–3 ASMs were enrolled. Total concomitant ASM drug load (not including cenobamate) was calculated by dividing the patient’s prescribed dose for each ASM by its defined daily dose, a World Health Organization standardized daily maintenance dose, then summing the ratios. Changes in concomitant ASM drug load were measured from baseline in 3-month intervals up to 24 months by both total and class-specific ASM drug load. Subgroups of interest included: older adults (65–70 years), prior epilepsy-related surgery vs none, and baseline seizure frequency &lt;3 vs ≥3 seizures/28 days. <h3>Results:</h3> Data from 240 patients were available (median exposure duration 30.2 months, mean age 41.8 years, mean baseline drug load 3.57). Following cenobamate initiation, mean percent reductions in concomitant ASM drug load occurred at Month 12 (29.44%) and 24 (31.82%), and in all assessed ASM drug classes, with the largest reduction in benzodiazepines (55.24% at Month 24). All assessed patient subgroups exceeded 30% reduction in concomitant ASM drug load at Month 24. Patients with low (−0.25 to &lt;0), moderate (−0.59 to −0.25), or high (−3.3 to −0.59) change in concomitant ASM drug load vs no change, respectively, had similar maintenance of ≥50% (89.29%, 86.42%, 90.57% vs 85.99%) and 100% response rates (80.65%, 84.29%, 70.00% vs 82.00%). <h3>Conclusions:</h3> Adding cenobamate led to reduced mean concomitant ASM drug load during Year 1 and Year 2. Reductions occurred regardless of ASM drug class, patient age, or epilepsy disease characteristics. Reductions in ASM drug load did not impact maintenance of response rates. See also abstract by O’Dwyer et al. <b>Disclosure:</b> Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Aboumatar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion. Louis Ferrari has received personal compensation for serving as an employee of SK Life science. Mr. Stern has received personal compensation for serving as an employee of SK Life Science. Mr. Wade has nothing to disclose. Dr. Weingarten has received personal compensation for serving as an employee of SK Life Science. The institution of Dr. Connor has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for SK Life Sciences. The institution of Dr. Connor has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Sciences. The institution of Dr. Rosenfeld has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for SK Life Science. Dr. Rosenfeld has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Science. The institution of Dr. Rosenfeld has received research support from SK Life Science. The institution of Dr. Rosenfeld has received research support from UCB Pharma.