Adjuvant Cenobamate Shows Significant Reductions in Seizures and Hospitalizations in Severe Refractory Epilepsy

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A recent 6-month cohort study presented at the 2023 AES Annual Meeting demonstrated that adjuvant cenobamate significantly reduced seizures in patients with severe refractory focal epilepsy and suggested potential benefits in hospitalization rates.

 Shanika Samarasekera, MBBS, FRCP, a consultant neurologist, neurology department, University Hospitals Birmingham

Shanika Samarasekera, MBBS, FRCP

New findings from a retrospective cohort study showed that adjuvant cenobamate (Xcopri; SK Life Science), an FDA-approved treatment, reduced seizure burden in the majority of patients with severe refractory focal epilepsy and demonstrated potential favorable impact on rates of hospitalization.1 Presented at the 2023 American Epilepsy Society (AES) annual meeting, held December 1-5, in Orlando, Florida, these results suggest that cenobamate reduced seizures as well as hospitalization, and recommends that pharmacy support needs to be accessible as service utilization increases.

Among 61 patients (male, n = 34) with severe refractory epilepsy, 56 (92%) participants reported a seizure duration of over 10 years. At baseline, a total of 37 (60%) patients were on the epilepsy surgery pathway and were prescribed at least 3 concomitant antiseizure medications (ASMs). Following the administration of cenobamate, 25 patients (40%) were able to withdraw 1 concomitant ASM and 3 patients were able to withdraw 2 ASMs.

Clinical Takeaways

  • Adjuvant cenobamate demonstrated significant efficacy in reducing seizure frequency, presenting a potential breakthrough for patients with severe refractory focal epilepsy.
  • The addition of cenobamate not only contributed to reduced hospitalization rates but also prompted an increase in patient contact with epilepsy services.
  • These findings underscore the importance of proactive pharmacy support as cenobamate becomes a pivotal element in the evolving landscape of severe epilepsy treatment.

This study was conducted by colead authors Shanika Samarasekera, MBBS, FRCP, a consultant neurologist, and Shehr Syeda, MBBS, MRCP, internal medicine trainee (CT1 IMT), both from the neurology department at University Hospitals Birmingham. In this study, investigators explored whether cenobamate reduced seizures in adults who have been considered for epilepsy surgery as well as if the addition of cenobamate impacted hospitalizations and contact with epilepsy services. The researchers assessed records of patients commenced on adjunctive cenobamate between January and mid-August 2022.

In the 6-month period of the study, a total of 50 patients (80%) achieved a reduction in seizure frequency and 26 patients (42%) achieved significant seizure reduction (over 50%), of whom 3 were seizure-free. The authors noted that the maximum dose of cenobamate used among the patient population sample was 200 mg/day. Notably, the addition of cenobamate was associated with reduced hospitalization in 15 patients (25%), and contact with services through the epilepsy specialist nurses increased in 37 patients (61%), with the most common query being about dose titration.

READ MORE: Fetal Outcomes Largely Unaffected by Antiseizure Medication Lacosamide

In another study on cenobamate presented at AES 2023, new pharmacokinetic (PK) and pharmacodynamic (PD) data showed that earlier adjustments of concomitant ASM improved patient retention to cenobamate.1 These findings from a post-hoc analysis of the phase 3, open-label Study C021 (NCT02535091) support the notion that dosages of adjunctive ASMs should be adjusted early in the treatment course with cenobamate and also inform recommendations for even earlier and larger reductions of these therapies in the clinical setting.3,4

Presented by senior author William E. Rosenfeld, MD, FAAN, FAES, neurologist from the Comprehensive Epilepsy Care Center for Children and Adults, in St. Louis, Missouri, and colleagues, investigators examined the dose adjustments of concomitant ASMs of patients with uncontrolled focal seizures on cenobamate. In Study C021, increased doses of cenobamate (12.5, 25, 50, 100, 150, and 200 mg/day) were administered biweekly. Additional increases for patients were allowed to 400 mg/day in biweekly 50-mg/day increments as well as adjustments to concomitant ASMs.

Among 1340 patients included, CYP2C19 substrates clobazam (Onfi; Lundbeck), phenytoin, and phenobarbital had pharmacokinetic interactions with cenobamate and led to increased plasma exposure and early dose reductions. In week 52 of the study, the total clobazam dose was reduced by a mean of 30.9% and the total daily dose of lacosamide (Vimpat; UCB) decreased by 21.7% by visit 14. As the investigators gained more experience, it was noted that these dose reductions were made earlier and more proactively, which reflected current consensus recommendations.2

Click here for more coverage of AES 2023.

REFERENCES
1. Aung P, Syeda S, Samarasekera S. The Impact of Cenobamate in Severe Refractory Focal Epilepsy – Does It Reduce Hospitalizations?. Presented at: AES 2023; December 1-5; Orlando, FL. Abstract 3.275
2. Ferrari L, Kamin M, Rosenfeld W. Dose Reduction Timing for Concomitant Antiseizure Medications: Post-hoc Analysis of a Phase 3, Open-Label Study of Cenobamate for Treatment of Uncontrolled Focal Seizures. Presented at: AES 2023; December 1-5; Orlando, FL. Abstract 1.278
3. Rosenfeld WE, Abou-Khalil B, Aboumatar S, et al. Post hoc analysis of a phase 3, multicenter, open-label study of cenobamate for treatment of uncontrolled focal seizures: Effects of dose adjustments of concomitant antiseizure medications. Epilepsia. 2021;62(12):3016-3028. doi:10.1111/epi.17092
 4. Smith MC, Klein P, Krauss GL, et al. Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations. Neurol Ther. 2022;11(4):1705-1720. doi:10.1007/s40120-022-00400-5
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