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

Quality of life and synergistic combinations of antiseizure medication in patients treated with cenobamate in early therapy lines for focal-onset seizures. (PubMed, Epilepsy Behav) - "Our study provides evidence that CNB in early therapy lines for focal-onset seizures is associated with an increased HrQoL. Low-dose clobazam can wok synergistically with CNB. The combination with SV2A modulators showed a positive trend."

HEOR • Journal • CNS Disorders • Epilepsy

Expanding the toolkit: An update on the evolution of new therapies for Lennox-Gastaut Syndrome. (PubMed, Semin Pediatr Neurol) - "The purpose of this paper is to address three such aspects of treatment evolution for LGS: (1) To review data supporting the repurposing of existing drugs for use in LGS, specifically, perampanel and cenobamate. (2) To present recent (soticlestat), ongoing (carisbamate, bexicaserin, clemizole) and upcoming (opakalim) clinical drug trials for LGS...With the richness of recent trial development for LGS combined with the nascence of clinical trials for specific genetic epilepsies comes a new era in which treatment options for LGS will continue to expand. Increasing understanding of the underlying genetic and molecular underpinnings of LGS should enable development of unique therapies, with the continued aims of sustained, durable seizure control and additional positive impact on central nervous system outcomes and beyond."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

On December 9, SK Biopharmaceuticals announced that its innovative epilepsy drug “Cenobamate“ and sleep disorder treatment “Solriamfetol“ have received New Drug Application (NDA) approval from the National Medical Products Administration (NMPA) of China. (The Asia Business Daily)

China approval • Epilepsy • Sleep Disorder

Cenobamate in adult patients with epilepsy and intellectual disability. (PubMed, Seizure) - "In adult PWE and intellectual disability, cenobamate is similarly efficacious and tolerated as in patients without ID."

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

Evaluating the impact of cenobamate in the management in patients with drug resistant focal epilepsy - A retrospective real world observational study of patients attending NHS Greater Glasgow and Clyde. (PubMed, Epilepsy Res) - "These results offer insights for clinicians regarding the real-world effectiveness, retention rates, and healthcare cost implications of CNB therapy in a cohort consisting largely of patients with severe drug resistant epilepsy. Further studies are ongoing to assess the efficacy of CNB when used earlier and also to provide a comprehensive assessment of health care resource use in this real world settings."

Journal • Observational data • Real-world evidence • Retrospective data • CNS Disorders • Epilepsy

Cenobamate for drug-resistant epilepsy: Initial experience from a single tertiary centre. (PubMed, Can J Neurol Sci) - No abstract available

Journal • CNS Disorders • Epilepsy

Psychiatric effects of cenobamate in adults with epilepsy: A retrospective study. (PubMed, Epilepsy Behav) - "Cenobamate did not induce new psychiatric side effects and was well tolerated in patients with pre-existing psychiatric conditions and normal intellectual functioning. However, in individuals with intellectual disabilities and baseline psychiatric comorbidities, CNB may exacerbate irritability through multifactorial mechanisms."

Journal • Retrospective data • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Psychiatry

Individual Alpha Frequency as an EEG Biomarker of Drug-Related Cognitive Burden in Epilepsy. (PubMed, Eur J Neurol) - "EEG background activity, assessed via IAF, is sensitive to cognitive impairment related to ASMs in PwE, demonstrated in both cross-sectional and longitudinal contexts. IAF is thus a promising, simple, cost-effective biomarker to monitor cognitive burden in clinical epilepsy management."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

Efficacy and safety of cenobamate in developmental and epileptic encephalopathies: A systematic review and meta-analysis. (PubMed, Seizure) - "Cenobamate demonstrates promising efficacy in highly refractory DEEs, with over half of patients achieving ≥50 % seizure reduction and ∼10 % attaining seizure freedom despite extensive prior treatment failures. The high retention rate and manageable safety profile support its use as a valuable therapeutic option in this difficult-to-treat population."

Journal • Retrospective data • Review • Ataxia • CNS Disorders • Epilepsy • Movement Disorders

EpiTrack: Direct and indirect role in the assessment of executive functions and memory - Systematic review. (PubMed, Appl Neuropsychol Adult) - "Perampanel and Cenobamate exhibited a neutral cognitive profile, with scores stable at "moderate impairment" (29.67-30.04). Lamotrigine and Levetiracetam demonstrated persistent severe impairment. Brivaracetam improved from severe to moderate impairment (not clinically significant). Only Topiramate showed a clinically significant decline (30.0 to 26.6)...In contrast, VNS with 3-4 AEDs maintained severe impairment. This review underscores the importance of accurate cognitive assessment in epilepsy management, with a monitoring frequency of no more than every six months for patients receiving AED therapy."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

Safety and Effectiveness of Cenobamate in Pediatric Patients with Epilepsy (AES 2025) - "Overall, our study showed that initiation of cenobamate as adjunctive therapy was effective and safe for pediatric patients with refractory epilepsy, with the goals of reducing seizure frequency and establishing improved seizure control."

Clinical • Anesthesia • CNS Disorders • Epilepsy • Pediatrics

Cenobamate in real world : a single center study (AES 2025) - "68 patients had a proactive decrease in one or several concomitant ASM dosage, mainly lacosamide (N=25), perampanel (N=14), clobazam (N=12). 51 patients needed a further decrease in other ASM dosage (mainly brivaracetam and lacosamide), and 52 patients could stop at least one concomitant ASM (mainly lacosamide and perampanel)... Efficacy of CNB is confirmed in this real world series of patients. After one year of follow up, the efficacy is maintained with 52% of the patients being either seizure free or responders. Side effects are common and in line with those found in regulatory studies."

Clinical • Real-world • Real-world evidence • Ataxia • CNS Disorders • Epilepsy • Movement Disorders

Corpus Callosotomy for Treatment of Infantile Epileptic Spasms Syndrome: The UCLA Experience (AES 2025) - "Median number of prior anti-seizure medications was 8 (IQR 7 – 10), and all subjects failed to respond to a trial of standard first-line therapy (prednisolone, ACTH, vigabatrin, or a combination thereof)...Patient 2 achieved seizure-freedom (now >1 yr) in response to cannabidiol and clobazam, prior to proposed surgical resection...After relapse with tonic seizures and epileptic spasms, both patients have since responded to cenobamate and remain seizure-free > 1yr... This study suggests that corpus callosotomy may aid in treatment of children with IESS, though the response rate in this series is lower than prior reports (Baba et al, 2018). Nevertheless, CC appears to be helpful in a substantial minority of patients, and CC should perhaps be considered much earlier in the course of epilepsy. Further study is clearly warranted to identify best candidates for CC in the setting of IESS."

CNS Disorders • Epilepsy

Cenobamate and Brivaracetam Use in Pregnancy and Lactation - A Case Report (AES 2025) - "She previously failed multiple ASMs, including clonazepam, gabapentin, oxcarbazepine, levetiracetam, lamotrigine, zonisamide, and phenytoin, due to inadequate seizure control or intolerable side effects. This case describes a normal pregnancy outcome in a young female with intractable localization-related epilepsy on combination cenobamate and brivaracetam. To our knowledge, this is the first reported pregnancy outcome with this specific ASM combination. This offers reassuring, preliminary evidence that cenobamate and brivaracetam may be safely continued in pregnancy when benefits outweigh risks, especially in intractable epilepsy."

Case report • Clinical • Anesthesia • CNS Disorders • Epilepsy

Assessment of Adjunct Cenobamate on Seizure Outcome Using Long-term Electrocorticography (AES 2025) - "Table of Results LCM – Lacosamide ESL – Eslicarbazepine CBZ – Carbamazepine Long-term ECoG offers an objective method to assess antiseizure medication efficacy. Long-term ECoG offers an objective method to assess antiseizure medication efficacy. However, it also presents challenges such as inconsistent interrogation and uploads, resulting in a smaller sample size. In this retrospective analysis, 85% of patients treated with both CNB and RNS demonstrated a reduction in seizure count."

CNS Disorders • Epilepsy

Effect of Cenobamate on EEG Biomarkers in Adults with Drug-Resistant Focal Epilepsy: Intraindividual comparison (AES 2025) - "If confirmed in the full cohort, ΔPSWE may serve as a practical pharmacodynamic biomarker to monitor CNB response alongside seizure counts."

Biomarker • Clinical • Late-breaking abstract • CNS Disorders • Epilepsy

Potential Factors Affecting Length of Stay in Patients Undergoing Stereotactic Electroencephalogram (AES 2025) - "Opiates were converted to oral morphine milligram equivalents (OMME) and directly compared to patient's LOS...Subgroup analyses did not find that a specific opiate (i.e. hydromorphone versus hydrocodone) contributed more to a prolonged LOS than another...Cenobamate was also noted to be held on post-operative day 0 in these patients... Data analysis indicates that prolonged LOS may be influenced by multiple factors, including quantity of opiates and ASMs with prolonged half-lives. Initially we thought that specific mechanisms of action of opiates may be an influencing factor, however our results have not contributed to that conclusion at this time. Our results also clearly show that a prolonged length of stay is indeed secondary to delay in seizure occurrence which may be a result of the aforementioned factors."

Clinical • CNS Disorders • Epilepsy

Efficacy and Tolerability of RAP-219, a Potential First-in-Class Negative Allosteric Modulator of γ8 Transmembrane AMPA Receptor Associated Protein: Impact on RNS Long Episodes and Focal Seizures (AES 2025) - "Use of perampanel was exclusionary...The most common ASMs were lamotrigine, cenobamate, levetiracetam, zonisamide, and clobazam... The baseline characteristics of the patients enrolled in this innovative POC study testing the electrographic and clinical effect of RAP-219 in RNS patients with FOS are similar to those reported in contemporary Phase 2 and 3 studies. Efficacy, safety, and tolerability of RAP-219 (to be reported) as evaluated during the 8-week, open-label treatment trial are expected to be highly relevant to patients with drug-resistant FOS."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy

Multi-Night Analysis on the Effect of Epilepsy Medication on Sleep Spindles in Intracranial EEG (AES 2025) - "Each patient took between 1-4 anti-epilepsy medications, which included Lamotrigine, Topiramate, Cenobamate, Clobazam, Oxcarbazepine, Briviact, Carbamazepine, Lacosamide, and Zonisamide. This preliminary analysis into muti-medication effects on sleep spindles during a multi-night EMU stay with intracranial EEG, suggests that there could be a relationship between anti-epilepsy medication dosages and sleep spindle rates. If confirmed in a larger cohort, the observed increase in sleep spindle rate with higher medication doses might suggest a positive effect of medication on sleep. This could be an indirect consequence of the decrease in epileptiform activity, which might permit the augmentation of sleep spindles even outside the seizure onset zone."

CNS Disorders • Epilepsy

Extending Epilepsy and Pregnancy Registers: A Pilot in The UK Epilepsy and Pregnancy Register to Include Routine Longitudinal Child Follow Up (AES 2025) - "These numbers included rarer ASM exposures such as clobazam, cenobamate, zonisamide, lacosamide and brivaracetam. A dual model of both surveillance and enhanced investigations offers the opportunity to routinely collect screening level child health and neurodevelopmental outcome data across large geographical regions, alongside more enhanced researcher-led data collection for subpopulations. Implementing longitudinal routine child health and neurodevelopmental investigations into already established initiatives such as Epilepsy and Pregnancy Registers will improve available data regarding the safe use of ASMs in women of reproductive age."

Clinical • CNS Disorders • Epilepsy

Early Response Rates With Adjunctive Cenobamate in Uncontrolled Focal Seizures: Open-Label Extension of a Randomized Clinical Study in a Multinational Asian Population (AES 2025) - "As patients initially randomized to PBO during the DB study were converted to CNB during the OLE, early seizure reductions and treatment responses occurred in pattern generally similar to that observed in all CNB patients during the initial DB titration. This further supports that positive responses to CNB may be observed early during the currently approved titration schedule."

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

Sacred Obsessions and Seizures: A Case of Scrupulosity in Right Temporal Lobe Epilepsy (AES 2025) - "She remained largely seizure-free from 2004 until 2019 with her anti-seizure medications narrowed to levetiracetam monotherapy...She reported also worsening auras at this time.After psychiatric stabilization, due to the ongoing breakthrough seizures, cenobamate was initiated... This case highlights a compelling link between TLE and scrupulosity-type OCD. The relationship between focal epilepsy and obsessive religious ideation suggests shared pathophysiologic mechanisms involving limbic and fronto-temporal networks (Kaplan, 2011; Devinsky & Schachter, 2009). These findings reinforce prior associations between TLE and interictal hyperreligiosity (Waxman & Geschwind, 1975; Aycicegi-Dinn et al., 2008) and support the need for integrated neuropsychiatric care in epilepsy."

Clinical • CNS Disorders • Epilepsy • Insomnia • Obsessive-Compulsive Disorder • Psychiatry • Sleep Disorder

Fenfuramine for adults with Lennox-Gastaut Syndrome - What is the impact? (AES 2025) - "Greatest efficacy was seen in those prescribed both Cenobamate and Fenfluramine. Fenfluramine appears to be efficacious in reducing convulsive seizures for those adults with highly refractory epilepsy in the context of LGS. Addition of Fenfluramine contributed to a substantial reduction in hospitalisations, with associated health-economic benefits. Assessment of efficacy needs to be individualised to reflect the variability in seizure pattern and frequency in this highly refractory population."

Clinical • CNS Disorders • Epilepsy

Long-Term Efficacy of Adjunctive Cenobamate: Open-Label Extension of a Randomized Clinical Study in a Multinational Asian Population (AES 2025) - "Reductions in seizure frequency increased or were maintained during the 32-week OLE maintenance phase. The safety profile during long-term treatment was generally consistent with the DB phase. These results support the long-term efficacy of CNB in adult patients with uncontrolled focal seizures."

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

Neurobeachin (NBEA) Gene Defect Associated Epileptic Encephalopathy: Responsiveness to Cenobamate (AES 2025) - "Cenobamate was titrated every two weeks at age 13 years, and patient became seizure free at a dose of 100mg daily, and was tapered off clobazami after several months being seizure free, he remains delayed in academics but less autistic like and fewer behavioral issues on daily fenfluramine(24mg) , valproate (1350mg), and cenobamate (100mg) at 50.8 kg.Patient 2 : 32 year old female diagnosed NBEA with epilepsy and autism at age 2 years with comorbid mood disorder, refractory epilepsy...She was started on cenobamate and tapered off oxtellar and continued valproate and lorazepam... NBEA is a rare DEE with refractory epilpesy and identification can lead to better treatment outcomes. Cenobamate therapy in two cases improved both seizure control and behavioral outcome. More research is warranted."

Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Mood Disorders • Ophthalmology • Psychiatry • NBEA