Xcopri (cenobamate) / SK Bio, Angelini Group, Endo, Ono Pharmaceutical, Eurofarma, Dong-A - LARVOL DELTA

Valproate-Associated Hyperammonemic Encephalopathy Despite Nontoxic Serum Levels and Preserved Liver Function: A Case Report. (PubMed, Cureus) - "We report a 49-year-old man with intellectual disability and long-standing drug-resistant epilepsy treated with valproate, phenytoin, phenobarbital, cenobamate, levetiracetam, and several psychotropic medications. This was followed by sustained neurological recovery and a decrease in serum ammonia to 43.1 µmol/L. This case emphasizes the importance of measuring serum ammonia in patients receiving valproate who develop otherwise unexplained altered mental status, particularly in the setting of intellectual disability and extensive antiseizure polytherapy."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Immunology • Mental Retardation

SK Biopharmaceuticals…said on the 16th that its Japanese partner Ono Pharmaceutical obtained new drug approval from Japan's Ministry of Health, Labour and Welfare (MHLW) for the epilepsy drug "Cenobamate (Japanese product name Xcopri)." (Chosun Biz) - "The approval was based on the results of a multinational phase 3 trial conducted in Korea, China and Japan in adults with focal-onset seizures whose seizures were not controlled by existing antiepileptic treatments."

Japan approval • Epilepsy

Cognitive Side Effects of Antiseizure Medications in Adults with Epilepsy: An Update with a Focus on New Therapeutic Agents. (PubMed, CNS Drugs) - "Overall, newer-generation ASMs, including rufinamide, lacosamide, brivaracetam, cannabidiol, fenfluramine, and ganaxolone, demonstrate generally favourable cognitive profiles when used at recommended doses, particularly in monotherapy or rational polytherapy. Eslicarbazepine and cenobamate may be associated with mild, dose-dependent cognitive effects, occurring only at the upper end of the recommended dose range. In contrast, old ASMs and certain second-generation agents, notably topiramate and zonisamide, remain consistently associated with higher cognitive risks...Cognitive dysfunction in epilepsy is multifactorial, reflecting the interaction between disease-related neurobiological mechanisms and treatment effects. Optimal management requires balancing seizure control with cognitive preservation through individualised drug selection, cautious titration, and minimisation of polytherapy to achieve the best functional and quality-of-life outcomes."

Adverse events • Journal • Review • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Mental Retardation

Cenobamate Improves Emotional Dysregulation, Impulsivity, and Apathy in Drug-Resistant Focal Epilepsy: A Longitudinal Neuropsychological Study. (PubMed, Neurol Ther) - "Adjunctive CNB was correlated with psychopathological improvements alongside domain-specific cognitive changes, independent of seizure outcome and concomitant ASM burden. These findings further expand current knowledge on CNB impact and tolerability profile."

Journal • CNS Disorders • Depression • Epilepsy • Mood Disorders • Psychiatry

Antiseizure Medications in Development: Novel Mechanisms, Precision Therapy, and the Move Towards Disease Modification. (PubMed, Curr Issues Mol Biol) - "Functional-state-selective sodium channel modulation has emerged as a leading conceptual advance supported by converging mechanistic and early clinical evidence, exemplified by relutrigine (PRAX-562), a preferential persistent-current inhibitor for which a regulatory decision is pending in SCN2A/SCN8A-DEEs, and vormatrigine (PRAX-628), whose large open-label effect was not reproduced in a controlled (blinded) trial...Parallel advances include the selective Kv7 opener azetukalner; the dual-mechanism benchmark cenobamate; cholesterol-24-hydroxylase inhibition (soticlestat); selective serotonergic agonism (bexicaserin); glutamatergic precision agents (radiprodil); subtype-selective GABAA modulators (darigabat, ganaxolone); and gene-directed therapies (zorevunersen, elsunersen)... The pipeline reflects an ongoing shift from broad symptomatic agents toward mechanism-led, genotype-matched, and potentially disease-modifying treatments. This shift is tempered by a persistent..."

Journal • Review • CNS Disorders • Epilepsy • SCN8A

Narrative Review: Efficacy, Safety, and Tolerability of Newer Third-Generation Antiseizure Medications for Focal Epilepsy: A New Benchmark in Treatment Outcomes? (PubMed, Neurol Ther) - "All third-generation ASMs were effective adjunctive therapies. Cenobamate was associated with higher responder and seizure freedom rates and higher long-term retention rates. Brivaracetam and lacosamide had favorable tolerability profiles. The notable seizure freedom rates with cenobamate suggest a potential new benchmark in focal seizure treatment. Comparator trials are needed to confirm possible efficacy and tolerability differences among third-generation ASMs."

Journal • Review • CNS Disorders • Eosinophilia • Epilepsy • Fatigue • Pain • Psychiatry

Pediatric developmental epileptic encephalopathies treated with cenobamate: Real-world outcomes across etiologies, syndromes, and seizure types. (PubMed, Epilepsia) - "CNB was associated with sustained effectiveness and acceptable tolerability across pediatric DEEs. Slow weight-based titration and proactive simplification of sodium channel blockers and clobazam may optimize benefit-risk."

Journal • Real-world evidence • CNS Disorders • Epilepsy • Pediatrics

Long-term efficacy of adjunctive cenobamate: Open-label extension of a randomized, placebo-controlled study in a multinational Asian population. (PubMed, Epilepsia) - P3 | "The high long-term seizure frequency reductions, including a 100% responder rate of 25.5%, were consistent with previous long-term cenobamate efficacy. The OLE safety profile was also generally consistent with the known cenobamate safety profile, with no new safety signals identified. These results support the use of cenobamate in adult Asian patients with uncontrolled focal seizures."

Clinical • Journal • CNS Disorders • Eosinophilia • Epilepsy • Infectious Disease • Novel Coronavirus Disease

Advances in Sodium Channel Modulation in Epilepsy Therapy: Focus on Eslicarbazepine, Lacosamide and Cenobamate. (PubMed, Biomedicines) - " Recent advances in sodium channel modulation have expanded therapeutic options for focal epilepsy and support the development of more selective, mechanism-based ASM therapies. Eslicarbazepine acetate, lacosamide, and cenobamate demonstrate favorable efficacy and tolerability profiles and may improve seizure control in patients with drug-resistant epilepsy."

Journal • Review • Cardiovascular • CNS Disorders • Epilepsy • Fatigue • Heart Failure

Pharmacokinetics, Safety, and Dosing of Antiseizure Medications in Patients with Renal or Hepatic Impairment. (PubMed, Clin Pharmacokinet) - "Ten newer antiseizure medications (ASMs) approved since 2000 and selected for this review (cenobamate, brivaracetam, eslicarbazepine acetate, lacosamide, perampanel, fenfluramine, ganaxolone, cannabidiol, stiripentol, and rufinamide) have broadened treatment options for drug-resistant epilepsy. Regulatory discrepancies between FDA and EMA labeling were identified for all ten agents, notably divergent hepatic dose caps for perampanel and cenobamate, conflicting renal recommendations for fenfluramine, and discordant guidance for eslicarbazepine acetate in severe renal impairment. These agents exhibit no uniform class effect in organ impairment; prescribing must be governed by agent-specific disposition profiles, organ-function severity, and free-drug monitoring for highly protein-bound agents like perampanel and ganaxolone."

Journal • PK/PD data • Review • CNS Disorders • Epilepsy • Hepatology • Nephrology • Renal Disease

DECREASE study: A European pool-analysis of patients with significant reductions in concomitant antiseizure medications in cenobamate Early Access Programs. (PubMed, Epilepsia Open) - "People with highly drug-resistant epilepsy often need to take several antiseizure medications at the same time. Combined data from European Early Access Programs show that about 10% of people treated with cenobamate were able to stop all other antiseizure medications or reduce treatment to cenobamate plus one other medication. Despite this simplification of treatment, one-third of these patients became seizure-free and more than two-thirds experienced at least a 50% reduction in seizure frequency. Within this group, no patients stopped cenobamate because of side effects."

Journal • CNS Disorders • Epilepsy • Fatigue • Otorhinolaryngology • Vertigo

Cenobamate and Trazodone Combination Suppresses Seizures, EEG Alterations, Preserves Neuronal Architecture and Normalizes the BDNF/TrkB Expression in PTZ‑Kindled Mice. (PubMed, Neurochem Res) - "Therefore, we investigated the effect of cenobamate (CNB, 30 mg/kg) and trazodone (TZ, 10 mg/kg), alone and in combination, in PTZ-kindling model, where mice received 11 doses of pentylenetetrazole (PTZ, 40 mg/kg) every other day for three weeks. These parallel findings suggest that positive allosteric GABAA modulation and persistent sodium-current inhibition by CNB, combined with TZ serotonergic modulation, reduce hyperexcitability, pathological neuroplasticity, and glial reactivity. Collectively, TZ + CNB is a promising mechanistically complementary regimen that suppresses seizure progression and associated molecular and neurostructural pathology, which needs further preclinical optimization and translational investigations."

Journal • Preclinical • CNS Disorders • Epilepsy • BDNF • GFAP • NTRK2

Beyond efficacy: defining the cenobamate response profile. (PubMed, Neurol Sci) - No abstract available

Journal

Exploring the impact of controlled substance restrictions on epilepsy care in the United States: A neurologist survey. (PubMed, Epilepsy Behav) - "Respondents reported high rates of medication access issues related to controlled substance restrictions and low rates of ASM misuse. Controlled substance restrictions create practical barriers to reliably obtaining scheduled ASM prescriptions that can result in increased risk of morbidity and mortality. Controlled substance restrictions warrant reevaluation for PWE given the specific risk-benefit tradeoffs for this life-threatening neurologic condition."

Journal • CNS Disorders • Epilepsy

Sustained seizure reduction, treatment simplification, and high retention with cenobamate: A 12-month real-world study in refractory and ultra-refractory focal epilepsy. (PubMed, Epilepsia Open) - "In this real-world cohort of adults with drug-resistant focal epilepsy, CNB was associated with sustained seizure reduction, high 12-month retention rate, and acceptable tolerability, while most patients were maintained on a low concomitant ASM burden during follow-up. Improvement was observed even in highly treatment-experienced patients, although outcomes were more favorable in those with lower prior ASM burden, supporting the hypothesis that earlier CNB positioning may provide greater efficacy."

Journal • Real-world evidence • CNS Disorders • Epilepsy • Otorhinolaryngology • Vertigo

Effect of Concomitant Medications on Adverse Event Frequency, Severity, and Time to Resolution in a Cenobamate Open-Label Trial. (PubMed, Eur J Neurol) - "Patients taking fewer concomitant ASMs reported better tolerability as evidenced by fewer and less severe AEs and faster time to resolution. These findings emphasize the importance of optimizing concomitant ASM regimens through dose adjustments, ASM substitution, and treatment simplification to improve tolerability."

Adverse events • Journal • CNS Disorders • Epilepsy • Fatigue • Pain

Optimizing Drug-Resistant Epilepsy Management: Cenobamate's role in the Surgery/Neuromodulation Pathway. (PubMed, Drugs R D) - No abstract available

Journal • CNS Disorders • Epilepsy

Use of Cenobamate in a patient with Super-Refractory Status Epileticus (EAN 2026) - No abstract available

Clinical

Evaluating Gender Related Outcomes with Adjunctive Cenobamate in Focal-Onset Seizures (EAN 2026) - "Cenobamate demonstrated consistent efficacy and a similar tolerability profile in both females and males. Although small numerical differences were observed, no clear meaningful sex related differences emerged. These findings suggest that treatment-benefit from CNB is not sex dependent."

CNS Disorders • Epilepsy

Pharmacokinetics of Cenobamate in Focal Epilepsy: Influence of Sex and Concomitant Antiseizure Medications (EAN 2026) - "Regarding drug interactions, higher CNB concentrations were observed in patients co-treated with lacosamide ( p = 0.0335), while concomitant topiramate was associated with lower exposure ( p = 0.0044). The pharmacokinetics of cenobamate appear highly variable and are influenced by sex and concomitant ASMs. These findings highlight the importance of therapeutic drug monitoring and individualized titration strategies to optimize efficacy and safety in real-world clinical practice."

PK/PD data • CNS Disorders • Epilepsy • KEAP1

Real-world use of Cenobamate in pediatric drug-resistant epilepsy: A European multicenter retrospective study. (PubMed, Epilepsia Open) - "Side effects were common but usually mild, and most patients continued treatment long term. These results suggest cenobamate may be a useful option in pediatric drug-resistant epilepsy, but prospective studies are needed to confirm safety and effectiveness."

Clinical • Journal • Real-world evidence • Retrospective data • CNS Disorders • Epilepsy • Fatigue • Otorhinolaryngology • Pediatrics • Vertigo

Clinical Outcomes of Adult-Initiated Cenobamate in Developmental and Epileptic Encephalopathy Versus Other Drug-Resistant Epilepsies (EAN 2026) - No abstract available

Clinical • Clinical data • CNS Disorders • Epilepsy

Time to Pre-Randomization Monthly Seizure Frequency for Patients with Uncontrolled Focal Onset Seizures Treated with Cenobamate (EAN 2026) - "Cenobamate significantly prolonged the time to pre randomization monthly seizure rate and reduced the proportion of patients reaching it compared with placebo in a dose-dependent manner. Consistent with previously reported outcomes, higher CNB doses resulted in greater effects. These findings support time to baseline seizure rate as a promising endpoint for future epilepsy trials."

Clinical • CNS Disorders • Epilepsy

Efficacy and safety of adjunctive cenobamate in patients with intellectual disability: a real world experience (EAN 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Developmental Disorders • Mental Retardation

Exploring the Role of Early Add-On Cenobamate in Uncontrolled Focal Epilepsy: A Critical Appraisal of the Evidence. (PubMed, Neurol Ther) - "Cenobamate may offer substantial benefit in adults with uncontrolled focal epilepsy, with a favorable efficacy-tolerability balance, high retention, and possible advantages when introduced earlier (after two ASMs). Its interaction profile underscores the importance of careful management of concomitant ASMs. Because the comparative signals derive largely from non-randomized data, prospective controlled research is needed to confirm any benefit of early use and to better characterize long-term cognitive and psychiatric effects."

Clinical • Journal • Review • CNS Disorders • Epilepsy • Psychiatry