Comfyde (carisbamate) / J&J, SK Bio - LARVOL DELTA

Recent Advances in Ionic Mechanisms in Pituitary Cells: Implications for Electrophysiological and Electropharmacological Research. (PubMed, J Clin Med) - "The presence of esaxerenone, an antagonist of the aldosterone receptor, directly suppresses the magnitude of peak and late INa. Risperidone, an atypical antipsychotic agent, is effective at suppressing the IK(erg) amplitude directly, and di(2-ethylhexyl)-phthalate suppressed IK(erg). Solifenacin and kynurenic acid can interact with the KM channel to stimulate IK(M), while carisbamate and cannabidiol inhibit the Ih amplitude activated by sustained hyperpolarization. Moreover, the presence of either rufinamide or QO-40 can enhance the activity of single BKCa channels. To summarize, alterations in ion currents within native pituitary cells or pituitary tumor cells can influence their functional activity, particularly in processes like stimulus-secretion coupling. The effects of small-molecule modulators, as demonstrated here, bear significance in clinical, therapeutic, and toxicological contexts."

Journal • Review • CNS Disorders • Endocrine Cancer • Oncology • Pituitary Gland Carcinoma

Carisbamate Treatment of Adult and Pediatric Patients With Lennox-Gastaut Syndrome: A Phase I Pharmacokinetic Dose-Escalation Study (AAN 2025) - "Carisbamate exhibited linear, dose-proportional PK after SD and MD in pediatric and adult patients with LGS and was generally safe and well-tolerated. PopulationPK modeling showed that adult dosing regimens were appropriate for patients ≥12 years of age whereas dosing for patients ages 4 to <12 should be weight-based."

Clinical • P1 data • PK/PD data • CNS Disorders • Epilepsy • Pediatrics

Carisbamate Treatment of Adult and Pediatric Patients with Lennox-gastaut Syndrome: A Phase I Pharmacokinetic Dose-escalation Study (AES 2024) - P3 | "Carisbamate exhibited linear, dose-proportional PK after single and multiple dosing in pediatric and adult patients with LGS. Treatment with carisbamate was generally safe and well-tolerated, with nervous system adverse events most common. PopPK modeling showed that adult dosing regimens were appropriate for patients ≥12 years of age whereas dosing for patients ages 4 to < 12 should be weight-based."

Clinical • P1 data • PK/PD data • Anesthesia • CNS Disorders • Epilepsy • Novel Coronavirus Disease • Pediatrics

Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: SK Life Science, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy • Pediatrics

Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults (clinicaltrials.gov) - P3 | N=252 | Recruiting | Sponsor: SK Life Science, Inc.

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Pharmacological diversity amongst approved and emerging antiseizure medications for the treatment of developmental and epileptic encephalopathies. (PubMed, Ther Adv Neurol Disord) - "Rufinamide, fenfluramine, stiripentol, cannabidiol and ganaxolone are antiseizure medications (ASMs) with diverse mechanisms of action that have been approved for treating specific DEEs...Stiripentol is licensed for treating seizures associated with Dravet syndrome in patients taking clobazam and/or valproate...Greater understanding of the causes of DEEs has driven research into the potential use of other novel and repurposed agents. Putative ASMs currently in clinical development for use in DEEs include soticlestat, carisbamate, verapamil, radiprodil, clemizole and lorcaserin."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Psychiatry • GPR55 • SLC29A1

Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control. (PubMed, Biomedicines) - "Brivaracetam, a chemical analog of levetiracetam known to be a ligand for synaptic vesicle protein 2A, could directly suppress the I magnitude. Carisbamate, an anticonvulsant agent, not only inhibited the I amplitude but also reduced the strength of voltage-dependent hysteresis (Hys) associated with I. Cilobradine, similar to ivabradine, inhibited the amplitude of I; however, it also suppressed the amplitude of delayed-rectifier K currents. Dexmedetomidine, an agonist of α2-adrenergic receptor, exerted a depressant action on I in a concentration-dependent fashion...Lutein, one of the few xanthophyll carotenoids, was able to suppress the I amplitude as well as to depress Hys's strength of I. Pirfenidone, a pyridine derivative known to be an anti-fibrotic agent, depressed the I magnitude in a concentration- and voltage-dependent fashion. Tramadol, a synthetic centrally active analgesic, was shown to reduce the I magnitude, independent of its interaction with opioid..."

Journal • Review • Addiction (Opioid and Alcohol) • Fibrosis • Pain

Concerted suppressive effects of carisbamate, an anti-epileptic alkyl-carbamate drug, on voltage-gated Na and hyperpolarization-activated cation currents. (PubMed, Front Cell Neurosci) - "However, CRS strongly decreased the strength (i.e., Δarea) of the nonlinear window component of I (I), which was activated by a short ascending ramp voltage (V); the subsequent addition of deltamethrin (DLT, 10 μM) counteracted the ability of CRS (100 μM, continuous exposure) to suppress I. CRS strikingly decreased the decay time constant of I evoked during pulse train stimulation; however, the addition of telmisartan (10 μM) effectively attenuated the CRS (30 μM, continuous exposure)-mediated decrease in the decay time constant of the current...For I, CRS altered the steady-state I-V relationship and attenuated the strength of voltage-dependent hysteresis (Hys) activated by an inverted isosceles-triangular V. Moreover, the addition of oxaliplatin effectively reversed the CRS-mediated suppression of Hys. The predicted docking interaction between CRS and with a model of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel or between CRS and the hNa1.7..."

Journal • CNS Disorders • Epilepsy

Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: SK Life Science, Inc. | Trial completion date: Dec 2022 ➔ Jul 2023

Trial completion date • CNS Disorders • Epilepsy • Pediatrics

Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: SK Life Science, Inc. | Recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy • Pediatrics

SK Biopharmaceuticals begins domestic clinical trial for new epilepsy drug (Korea Biomedical Review) - "The Ministry of Food and Drug Safety approved the phase 3 clinical trial of SK Biopharmaceuticals' Carisbamate (YKP509)...SK Life Science, the US branch of SK Biopharmaceuticals, conducts the global clinical trial of Carisbamate, according to the company....Kyungpook National University Chilgok Hospital, Samsung Medical Center, and Seoul National University Hospital will carry out the trial....It is now recruiting patients in eight hospitals in the US and Colombia. The company seeks to recruit 252 patients to complete the trial by January 2025."

New P3 trial • Trial completion date • CNS Disorders • Epilepsy

Current and future pharmacotherapy options for drug-resistant epilepsy. (PubMed, Expert Opin Pharmacother) - "Current pharmacotherapy options for drug-resistant epilepsy include perampanel, brivaracetam and the newly approved cenobamate for focal epilepsies; cannabidiol (Epidiolex) for Lennox-Gastaut Syndrome (LGS), Dravet and Tuberous Sclerosis Complex (TSC); fenfluramine for Dravet syndrome and ganaxolone for seizures in Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder...For adult focal epilepsies, padsevonil and carisbamate are at a more advanced Phase III stage of clinical development followed by compounds at Phase II like selurampanel, XEN1101 and JNJ-40411813. For specific epilepsy syndromes, XEN 496 is under Phase III development for potassium voltage-gated channel subfamily Q member 2 developmental and epileptic encephalopathy (KCNQ2-DEE), carisbamate is under Phase III development for LGS and Ganaxolone under Phase III development for TSC. Finally, in preclinical models several molecular targets including inhibition of glycolysis, neuroinflammation and sodium..."

Journal • CNS Disorders • Epilepsy • Genetic Disorders • Immunology • Inflammation

Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults (clinicaltrials.gov) - P3 | N=252 | Recruiting | Sponsor: SK Life Science, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy

Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: SK Life Science, Inc. | Recruiting ➔ Active, not recruiting | N=30 ➔ 15

Enrollment change • Enrollment closed • CNS Disorders • Epilepsy • Pediatrics

Epilepsy: Expert opinion on emerging drugs in phase 2/3 clinical trials. (PubMed, Expert Opin Emerg Drugs) - "Novel mechanisms of action involve cholesterol degradation, mitochondrial pathways, anti-inflammation and neuro-regeneration. Earlier identification of genetic conditions through genetic testing will allow for earlier use of disease specific and disease-modifying therapies."

Journal • P2/3 data • CNS Disorders • Epilepsy • Immunology • Inflammation

Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: SK Life Science, Inc. | Trial primary completion date: Dec 2021 ➔ Apr 2022

Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics

Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults (clinicaltrials.gov) - P3 | N=252 | Not yet recruiting | Sponsor: SK Life Science, Inc.

New P3 trial • CNS Disorders • Epilepsy

SK Biopharmaceuticals starts P3 trials of YKP509 on applying for IND (Korea Biomedical Review) - SK Biopharmaceuticals...announced on the same day that it had just submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration."

IND • CNS Disorders • Epilepsy

SK life science Initiates Phase 3 Clinical Trial of Carisbamate for Lennox-Gastaut Syndrome (PRNewswire) - "SK Life Science, Inc...submitted a clinical study protocol to the U.S. Food and Drug Administration (FDA) for a Phase 3 clinical trial to evaluate the efficacy and safety of carisbamate for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS)....The Phase 3, global, multicenter, randomized, double-blind, placebo-controlled trial will evaluate the efficacy of two doses of carisbamate in more than 250 patients aged 4-55."

Clinical protocol • New P3 trial • CNS Disorders • Epilepsy

Carisbamate add-on therapy for drug-resistant focal epilepsy. (PubMed, Cochrane Database Syst Rev) - "The results suggest that carisbamate may demonstrate efficacy and tolerability as an add-on therapy for drug-resistant focal epilepsy. Importantly, the evidence for all outcomes except responder rate was of low to very low certainty, therefore we are uncertain of the accuracy of the reported effects. The certainty of the evidence is limited by the significant risk of bias associated with the included studies, as well as the statistical heterogeneity detected for some outcomes. Consequently, it is difficult for these findings to inform clinical practice. The studies were all of short duration and only included adult study populations. There is a need for further RCTs with more clear methodology, long-term follow-up, more clinical outcomes, more seizure types, and a broader range of participants."

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

Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: SK Life Science, Inc.; Trial completion date: Jun 2021 ➔ Jun 2022; Trial primary completion date: Jun 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Pediatrics

Carisbamate Safety Study in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: SK Life Science, Inc.; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Pediatrics

Bioavailability and Food Effect Study of 3 Types of Carisbamate (clinicaltrials.gov) - P1; N=33; Completed; Sponsor: SK Life Science, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Feb 2021 ➔ Oct 2021; Trial primary completion date: Feb 2021 ➔ Oct 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies. (PubMed, CNS Drugs) - "Six treatments are specifically indicated as adjunct therapies for the treatment of seizures associated with LGS in the US: lamotrigine, clobazam, rufinamide, topiramate, felbamate and most recently cannabidiol...Other treatments frequently used off-label include the broad spectrum anti-epileptic drugs (AED) levetiracetam, zonisamide and perampanel, while recent evidence from observational studies has indicated that a newer AED, the levetiracetam analogue brivaracetam, may be effective and well tolerated in LGS patients. Other treatments in clinical development include fenfluramine in late phase III, perampanel, soticlestat-OV953/TAK-953, carisbamate and ganaxolone...Because LGS is not a single entity, tailoring of treatment is needed as opposed to a 'one size fits all' approach. Further research is needed into the underlying aetiologies and pathophysiology of LGS, together with advancements in treatments that encompass the spectrum of seizures associated with..."

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

Carisbamate as a Potential Treatment for Alcohol Dependence (clinicaltrials.gov) - P1/2; N=11; Completed; Sponsor: Baylor College of Medicine; Active, not recruiting ➔ Completed; N=26 ➔ 11

Enrollment change • Trial completion • Addiction (Opioid and Alcohol) • Substance Abuse