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

Cenobamate reduces epileptiform activity in the ex vivo F98 rat glioma model. (PubMed, Front Neurosci) - "Our data show that cenobamate effectively reduced the epileptic phenotype in glioma-bearing brain slices. We hence suggest that cenobamate may effectively contribute to seizure control in tumor-associated epilepsy."

Journal • Preclinical • Brain Cancer • CNS Disorders • Epilepsy • Glioma • High Grade Glioma • Oncology • Solid Tumor

Efficacy, safety and tolerability of adjunctive cenobamate in pediatric and adult patients with Lennox Gastaut Syndrome. (PubMed, Epilepsy Behav) - "Our data suggest promising efficacy and good tolerability of adjunctive CNB treatment in LGS patients with varied etiologies. A prospective randomized controlled study of cenobamate in LGS patients is warranted."

Journal • Alzheimer's Disease • Ataxia • CNS Disorders • Cognitive Disorders • Epilepsy • Insomnia • Movement Disorders • Pain • Pediatrics • Sleep Disorder

Microglial activation is inhibited by selective anti-seizure medications. (PubMed, Inflamm Res) - "ASMs, applied to patients with DRE, have a differential ability to reduce microglial activation and pro-inflammatory microglial morphology in vitro. Moreover, sodium channel blockage modulates inflammation through microglia activation. Taken together these results suggest, that further investigation of patient's immune response to ASMs could be important."

Journal • CNS Disorders • Epilepsy • Inflammation • IFNB1 • NAV1 • PACERR • PTGS2 • TNFA

The Pharmacokinetic and Pharmacodynamic Relationship of Clinically Used Antiseizure Medications in the Maximal Electroshock Seizure Model in Rodents. (PubMed, Int J Mol Sci) - "We assessed the pharmacokinetic/pharmacodynamic (PK/PD) profiles of six ASMs, namely carbamazepine (CBZ), phenytoin (PHT), valproic acid (VPA), lacosamide (LSM), cenobamate (CNB), and retigabine (RTG), using MES models in mice and rats. These results suggest that rats may exhibit greater sensitivity to seizure protection in the MES model, likely reflecting species differences in metabolism and brain penetration. These findings highlight the value of considering concentration-response variations and species-specific differences when assessing the efficacy of both conventional ASMs and novel compounds exhibiting anticonvulsant activity."

Journal • PK/PD data • Preclinical • CNS Disorders • Epilepsy

Effectiveness and safety of adjunctive cenobamate in people with focal-onset epilepsy: Interim results after 24-week observational period from the BLESS study. (PubMed, Epilepsia) - P | "Cenobamate was effective in reducing seizure frequency in a real-world setting and showed a manageable safety profile. The treatment with cenobamate also reduced the burden of concomitant ASMs in both early and late users."

Journal • CNS Disorders • Epilepsy • Otorhinolaryngology

Cutaneous adverse reactions to low doses of cenobamate: don't DRESS it up…tell the truth! (PubMed, Neurol Sci) - No abstract available

Journal

Treatment of epilepsy using newer antiseizure medications: A retrospective cohort study of prescription patterns in Sweden 2013-2022. (PubMed, Epilepsia) - "Our observations indicate that prescription patterns of the newer ASMs comply with the currently approved indications for the respective medications for a majority of patients (prevalence of brivaracetam as adjunctive treatment is somewhat lower). Retention on the dispensed medications are in line with what would be expected for adjunctive treatment of patients with drug-resistant epilepsies."

Journal • Retrospective data • CNS Disorders • Epilepsy

Efficacy of cenobamate in tumor-related epilepsy. (PubMed, Epileptic Disord) - "This study demonstrates that adjunctive therapy with cenobamate treatment for TRE is a feasible and potentially effective option. Clinical history, including drug resistance, did not predict drug efficacy. No adverse effects were reported in those treated with chemotherapy. Further studies are needed to validate treatment response and safety."

Journal • Brain Cancer • CNS Disorders • Epilepsy • Oncology • Solid Tumor

Severe epilepsy phenotypes in adults with succinic semialdehyde dehydrogenase deficiency: Novel clinical and therapeutic insights from an Italian multicenter retrospective cohort study. (PubMed, Seizure) - "Epilepsy in SSADHD is believed to result from compensatory mechanisms within the GABAergic system. Cenobamate could have a therapeutic effect on patients with SSADHD by modulating GABAA receptors via a non-benzodiazepine site. However, this observation warrants further investigation, including potential benefits beyond seizure control. Epileptologists should consider SSADHD in patients with prolonged non-convulsive seizures or SE, especially when accompanied by developmental, movement, or psychiatric comorbidities and the characteristic neuroradiological features."

Journal • Retrospective data • Attention Deficit Hyperactivity Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Metabolic Disorders • Psychiatry

Cost-effectiveness analysis of cenobamate for epilepsy patients with drug-resistant focal onset seizures in the Netherlands. (PubMed, Expert Rev Pharmacoecon Outcomes Res) - "A Markov model was used tosimulate lifetime costs and quality-adjusted life years (QALYs) for cenobamatecompared to perampanel, brivaracetam, and lacosamide from the Dutch societalperspective. With the acknowledgment of the limitations, weconcluded that cenobamate is less costly and more effective, which can beconsidered a cost-effective treatment option for patients with drug-resistantfocal seizures in the Netherlands. Future real-world data are needed to confirmour findings."

HEOR • Journal • CNS Disorders • Epilepsy

Real-world use of cenobamate in pediatric focal epilepsies and developmental epileptic encephalopathies: A multicenter retrospective series. (PubMed, Epilepsia) - "CNB appears effective and well-tolerated in pediatric DRE, including DEE, with high retention and sustained efficacy over time. Adverse events were generally manageable with dose adjustments, and slow, weight-based titration improved tolerability. Prospective studies are warranted to confirm these findings."

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

Synergistic seizure reduction in patient with persistently elevated N-desmethylclobazam levels, CYP450 genetic polymorphism, and responsive neurostimulator targeting centromedian nuclei of bilateral thalami. (PubMed, Epilepsy Behav Rep) - "Clobazam (CLB) and cenobamate (CNB) are commonly used antiseizure medications (ASMs) in the treatment of patients with drug-resistant epilepsy (DRE). Pharmacogenetic testing revealed poor metabolism of CYP2C19, and N-CLB levels remained elevated and detectable for nearly one year after the discontinuation of treatment with CLB and CNB. Responsive neurostimulator (RNS) implantation within the bilateral centromedian nuclei (CMN) of the thalamus resulted in seizure freedom until N-CLB levels fell, after which there was an 83-93 % reduction in the frequency of generalized tonic-clonic seizures (GTC)."

Journal • CNS Disorders • Epilepsy • CYP2C19

Adverse Effects of Cenobamate in Pediatric Epilepsy: Demographic Considerations. (PubMed, J Child Neurol) - "Psychiatric adverse events were significantly associated with sex (100% female), χ2(1, N = 24) = 4.06, P = .04. Preliminary analyses also suggest older age (adolescence) may increase risk for psychiatric adverse events of cenobamate among patients with pediatric epilepsy."

Adverse events • Journal • CNS Disorders • Epilepsy • Pediatrics • Psychiatry

Rash and edema shortly after initial exposure to low dose cenobamate. (PubMed, Epilepsy Behav Rep) - "Rechallenging with CNB resulted in similar reactions. Our report aims at increasing awareness of these reactions to CNB."

Journal • CNS Disorders • Epilepsy

Comparative effectiveness of anti-seizure medications in emulated trials using medical informatics. (PubMed, Brain) - "For focal epilepsies, first-line ASMs achieved similar rates of seizure freedom, but levetiracetam remained superior to lamotrigine and oxcarbazepine for retention (p < 0.001); among second-line ASMs, topiramate and lacosamide were both superior to zonisamide for seizure freedom (p < 0.001), while lacosamide remained superior to topiramate and zonisamide for retention (p < 0.002); among third-line ASMs, cenobamate, brivaracetam, and clobazam achieved similar retention and seizure freedom. In conclusion, emulated clinical trials provide a useful framework for studying the comparative effectiveness of antiseizure medications using real-world observational data. Our findings of differences in seizure freedom and retention between ASMs help generate hypotheses that should be tested in future prospective, randomized comparative effectiveness trials."

HEOR • Journal • CNS Disorders • Epilepsy

Real-world retention of newer ASMs, including lacosamide and brivaracetam as first or second therapies in adult-onset epilepsy. (PubMed, Epilepsia) - "Lacosamide and brivaracetam have at least similar real-world retention as lamotrigine or levetiracetam when used early in adult-onset epilepsy. This widens the therapeutic arsenal and the possibility of tailored ASM selection."

Journal • Real-world evidence • CNS Disorders • Epilepsy

Acute dose-related effect of antiseizure medications on open field exploration of male rats with established epilepsy. (PubMed, Epilepsy Behav) - "This study investigated the acute effects of anticonvulsant doses of carbamazepine (CBZ), valproic acid (VPA), levetiracetam (LEV), and cenobamate (CNB) on locomotor activity and exploratory behavior in male rats 8-13 weeks after kainic acid (KA)-induced status epilepticus (SE) elicited confirmed spontaneous recurrent seizures (SRS) consistent with TLE. This study provides essential insight into the efficacy and tolerability profiles of a diversity of FDA-approved ASMs in a clinically relevant TLE model. Thus, SRS may influence ASM tolerability in preclinical TLE models used to inform clinical translation."

Journal • Preclinical • Anesthesia • Ataxia • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry

Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures (clinicaltrials.gov) - P3 | N=169 | Completed | Sponsor: SK Life Science, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy

Real-world utilization of Cenobamate as adjunct therapy in office-based neurology: practical tips and insights for titration. (PubMed, Front Neurol) - "The most common ASMs were voltage-gated sodium channel blockers (VGSC), Levetiracetam (LEV)/Brivaracetam (BRV) synaptic vesicle protein 2A (SV2A) inhibitors, and Perampanel (PER). It can be prescribed to patients on conventional therapy who are still having seizures and have failed two or more other ASMs. By reporting experiences of CNB titration, seizure, and drug load reduction outcomes in office-based neurology, this study will give German office-based outpatient neurologists evidence to support both CNB and other third-generation ASM use in their practice."

Journal • Real-world evidence • CNS Disorders • Epilepsy

Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy. (PubMed, Neurol Ther) - "Cenobamate represents a significant advancement in the treatment of drug-resistant focal epilepsy. Its early adoption in clinical practice has the potential to enhance patient outcomes. The expert panel provides recommendations that underscore individualized treatment planning, close monitoring during titration, and advocacy for improved accessibility. Continued research and policy initiatives are essential to fully realize the therapeutic potential of cenobamate."

Journal • CNS Disorders • Epilepsy

Cenobamate for Adjunctive Treatment in Adult and Pediatric Patients with Refractory Lennox-Gastaut Syndrome: A Retrospective Chart Review. (PubMed, Neurol Ther) - "This chart review provides promising evidence for the efficacy of CNB in treating LGS. Additional prospective studies will help to clarify CNB's efficacy and safety profile for patients with LGS."

Journal • Retrospective data • CNS Disorders • Epilepsy • Pediatrics

A french real-world experience with cenobamate in patients with drug-resistant focal epilepsy: A retrospective observational study. (PubMed, Epilepsy Behav Rep) - "Cenobamate is an effective and well-tolerated ASM in drug-resistant focal epilepsy and should be tried for highly drug-resistant epilepsy, even if many previous ASM have failed. Moreover, the impressive seizure-free rate leads to introducing cenobamate to all patients before or during the evaluation for surgical candidacy, and in any case before any resective surgery."

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

The Effectiveness of Cenobamate in Patients Treated With Vagus Nerve Stimulation for Drug Resistant Epilepsy. (PubMed, Eur J Neurol) - "For DRE patients treated with VNS who could benefit from further improvement in seizure control, adding CNB is useful. In our cohort, over one-third of patients experienced a meaningful improvement in seizure frequency with this recently marketed ASM."

Journal • Retrospective data • CNS Disorders • Epilepsy • Fatigue

Drug-induced subacute cutaneous lupus erythematous from cenobamate: case presentation and review of the literature. (PubMed, Dermatol Online J) - "The rash was initially treated with topical triamcinolone with improvement at one-month follow-up. Given the worsening rash, positive labs, and cenobamate as the only changed drug several months before initial onset, she was diagnosed with drug-induced subacute cutaneous lupus erythematous and her cenobamate was discontinued. To the best of your knowledge, this is the first reported case of a medication in the carbamate family leading to drug induced subacute cutaneous lupus erythematosus."

Journal • Review • CNS Disorders • Cutaneous Lupus Erythematosus • Dermatitis • Dermatology • Epilepsy • Immunology • Inflammatory Arthritis • Lupus

Budget impact analysis of cenobamate, a novel adjunctive therapy for the treatment of drug resistant focal onset seizures, from the Belgian healthcare payer perspective. (PubMed, J Med Econ) - "The savings at medical cost level fully offset the impact of cenobamate on the drug budget, leading to an overall healthcare budget saving of -€8 105 616 for NIHDI. This favourable outcome is largely due to cenobamate's high efficacy reflected in its high response rate and significant effect on reducing seizure frequency."

HEOR • Journal • CNS Disorders • Epilepsy