Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.

Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation.

Reductions in concomitant antiseizure medication drug load during adjunctive cenobamate therapy: Post-hoc analysis of a subset of patients from a phase 3, multicenter, open-label study.

Objective: Many patients with epilepsy require polytherapy, which increases their antiseizure medication (ASM) drug load, a measure that considers the doses of all ASMs a patient is taking. Changes in concomitant ASM drug load after adding cenobamate were evaluated post-hoc in a subset of the open-label, phase 3 study.

Methods: Patients 18-70 years old with uncontrolled focal seizures taking 1-3 ASMs were enrolled.

Cognitive and psychiatric adverse events during adjunctive cenobamate treatment in phase 2 and phase 3 clinical studies.

Objective: Cognitive and psychiatric adverse events in patients with epilepsy are important determinants of therapeutic outcomes and patient quality of life. We assessed the relationship between adjunctive cenobamate treatment and selected cognitive and psychiatric treatment-emergent adverse events (TEAEs) in adults with uncontrolled focal epilepsy.

Methods: This was a retrospective analysis of pooled populations of patients with focal epilepsy from two phase 2, randomized, double-blind clinical trials; two open-label extensions (OLEs) of those trials; and a long-term, open-label, phase 3 safety study.

Real-world analysis of retention on cenobamate in patients with epilepsy in the United States.

Background: This retrospective, observational study used US claims data to assess retention rates on cenobamate compared with four branded antiseizure medications (ASMs) in patients with epilepsy.

Methods: Adults (≥18 years) with prevalent epilepsy (ICD-10 code G40.xx) and ≥ 1 prescription for cenobamate or any of the newer branded ASMs (brivaracetam, eslicarbazepine, lacosamide, or perampanel) between May 1, 2020 and December 31, 2021 were identified from the HealthVerity Marketplace database.

Sustainability of seizure reduction and seizure control with adjunctive cenobamate: Post hoc analysis of a phase 3, open-label study.

Objective: In this post hoc analysis of a subset of patients from a long-term, open-label phase 3 study, we assessed ≥50%, ≥75%, ≥90%, and 100% seizure reduction and sustainability of these responses with cenobamate using a time-to-event analytical approach.

Methods: Of 240 patients with uncontrolled focal seizures who had adequate seizure data available, 214 completed the 12-week titration phase and received ≥1 dose of cenobamate in the maintenance phase (max dose 400 mg/day) and were included in this post hoc analysis. Among patients who met an initial given seizure-reduction level (≥50%, ≥75%, ≥90%, or 100%), sustainability of that response was measured using a time-to-event methodology.

Pharmacokinetics of cenobamate as monotherapy compared with adjunctive therapy.

Objective: Cenobamate was approved by the US Food and Drug Administration (FDA) based on studies of adjunctive therapy in patients with focal epilepsy. To support the use of cenobamate monotherapy, this pharmacokinetic (PK)-based simulation analysis evaluated the predicted PK exposure of cenobamate when used as monotherapy versus adjunctive therapy.

Methods: A population pharmacokinetic (PopPK) model of cenobamate was developed using pooled human data from eight phase 1 studies in healthy subjects or special populations, and three phase 2 and 3 studies in patients with focal seizures (N = 960).

Sudden unexpected death in epilepsy during cenobamate clinical development.

Objective: We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program.

Methods: We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic-clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic-clonic (PGTC) seizures who received ≥1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.

Post hoc analysis of a phase 3 study for treatment of uncontrolled focal seizures: Adjunctive cenobamate dose and seizure reduction by baseline seizure frequency.

This post hoc analysis (n = 240) of a subset of study sites (10 eligible US sites) from an open-label phase 3 study assessed whether baseline seizure frequency (<3 seizures/28 days vs ≥3 seizures/28 days) impacted mean cenobamate dose required to achieve 100% seizure reduction, duration of this response, and responder rates. Patients with uncontrolled focal seizures taking stable doses of 1-3 antiseizure medications were administered increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals.

Incidence of mental health conditions by seizure control among adults with epilepsy in the United States.

Background: Mental health conditions (MHCs) are frequent comorbidities among people with epilepsy; however, the influence of seizure control on the incidence of MHCs is not well reported. This retrospective observational cohort study based on claims data evaluated the effects of indicators of poor seizure control on the incidence of MHCs among MHC-naïve people with epilepsy. We hypothesized that poor seizure control is associated with new-onset MHC diagnoses and/or new prescription drugs for MHCs.

Efficacy of cenobamate by focal seizure subtypes: Post-hoc analysis of a phase 3, multicenter, open-label study.

Purpose: To report post-hoc efficacy data by focal seizure subtypes from 10 US study sites from a large, global, open-label, phase 3 study of adjunctive cenobamate.

Methods: Patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 antiseizure medications were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals (target dose 200 mg/day).

Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open-label study.

Objective: To report long-term post hoc efficacy and safety data from 10 US study sites from an open-label Phase 3 study of adjunctive cenobamate (NCT02535091).

Methods: Patients with uncontrolled focal seizures taking stable doses of 1-3 antiseizure medications (ASMs) were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day).

Efficacy of adjunctive cenobamate based on number of concomitant antiseizure medications, seizure frequency, and epilepsy duration at baseline: A post-hoc analysis of a randomized clinical study.

Background: In an 18-week, double-blind, placebo-controlled study (YKP3089C017; NCT01866111), cenobamate was effective for the treatment of focal-onset seizures. This post-hoc analysis examined the effects of baseline clinical features on the efficacy of adjunctive cenobamate during the study.

Methods: Adults with uncontrolled focal seizures despite treatment with 1-3 antiepileptic drugs/antiseizure medications (AEDs/ASMs) were randomized 1:1:1:1 to placebo or cenobamate 100, 200, or 400 mg once daily.

Incremental burden of mental health conditions in adult patients with focal seizures.

Introduction: Clinical research has consistently established mental health conditions (MHCs) as frequent comorbidities of epilepsy. However, the extent of economic burden of comorbid MHC in patients with focal seizures has not been systematically investigated. This retrospective cohort analysis of health plan claims compared healthcare use and costs among adult patients with focal seizures with and without comorbid MHC.

An Ex Vivo Evaluation of Cenobamate Administered via Enteral Tubes.

Background: Cenobamate is a new, Food and Drug Administration (FDA)-approved oral antiepileptic drug for treatment of focal seizures in adults. This study examined recovery of cenobamate from suspensions administered through ex vivo enteral feeding tubes.

Methods: Suspensions containing 100 and 200 mg of cenobamate were prepared (five duplicates for each dose), passed through five vertically standing tubes, and collected into flasks.

Reimplantation of an extruded osteoarticular segment of the distal tibia in a 14-year-old girl. Case report and review of the literature.

This case report describes the reimplantation of a 15-cm osteoarticular segment of the distal tibia in a 14-year-old girl who was hit by a truck. The bone fragment was debrided and reimplanted on the day of injury. A free flap was performed within 1 week.

Intramuscular lipoma of the supraspinatus causing impingement syndrome.

Impingement syndrome is a common ailment of the shoulder, particularly in individuals who perform repetitive overhead activities, such as athletes and laborers. Patients typically report progressive shoulder pain often exacerbated by flexion and abduction and may demonstrate a classic painful arc of motion. This article describes a case of a 45-year-old man with signs and symptoms consistent with impingement syndrome.