Cenobamate sNDAs seek PGTC and pediatric focal seizure indications

Adolescents and adults with primary generalized tonic-clonic (PGTC) seizures, and children with focal-onset seizures, could gain access to cenobamate under 2 supplemental new drug applications (sNDAs) now before the FDA.¹ SK Biopharmaceuticals announced November 4, 2026, that it filed an sNDA seeking a PGTC indication for patients aged 12 years or older, following an October submission to extend the drug's focal-onset seizure indication to pediatric patients.¹

Cenobamate (Xcopri) is currently approved in the US only for partial-onset seizures in adults.⁴ Donghoon Lee, CEO of SK Biopharmaceuticals, said the company is building on that foundation "by evaluating its potential in additional seizure types, age groups and formulations."¹

Cenobamate phase 3 trial design in PGTC seizures

The PGTC filing rests on a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT03678753) that enrolled 169 patients at 122 sites in 12 countries.¹ Eligible patients had idiopathic generalized epilepsy and at least 5 PGTC seizures during a 12-week baseline despite treatment with 1 to 3 antiseizure medications (ASMs).² Of those randomized, 135 were adults, and 34 were adolescents aged 12 to 17 years; adolescents received a weight-based oral suspension rather than tablets.²

Patients were randomized 1:1 to adjunctive cenobamate or placebo. Cenobamate was started at 12.5 mg/d, titrated over 10 weeks, and maintained at 200 mg/d (or a weight-based equivalent; minimum, 150 mg/d) during a 12-week maintenance phase.² Primary outcomes were median percent change in 28-day PGTC seizure frequency across the double-blind period and the 50% or greater responder rate during maintenance.²

Efficacy and safety of cenobamate for PGTC seizures

Median PGTC seizure frequency fell 71.9% from baseline with cenobamate vs 39.6% with placebo (P = .003).¹,² During maintenance, 71.1% of cenobamate-treated patients achieved a 50% or greater reduction vs 51.3% with placebo (P = .01), and 43.4% were seizure-free vs 20.5% (P = .002).²

Treatment-emergent adverse events occurred in 60.0% of patients receiving cenobamate and 53.0% receiving placebo, most commonly somnolence (16.5%) and fatigue (10.6%).² Investigators reported no treatment-related serious adverse events, deaths, or cases of drug reaction with eosinophilia and systemic symptoms (DRESS).² DRESS, including 1 fatality, occurred in earlier development with rapid titration, which is why labeling calls for starting at 12.5 mg once daily with increases every 2 weeks.⁴

Unmet need in PGTC seizures and pediatric focal epilepsy

PGTC seizures are considered the most serious generalized seizure type because of their association with seizure-related injury and sudden unexpected death in epilepsy (SUDEP).³ The trial population reflects that burden: every participant continued to have frequent convulsive seizures on an existing ASM regimen.² For pediatric clinicians, current labeling states that the safety and effectiveness of cenobamate in patients younger than 18 years have not been established.¹

The company said its pediatric focal-onset sNDA is supported by safety data from pediatric clinical trials, although the announcement did not specify the proposed age range or report efficacy outcomes.¹ A separate new drug application for an oral suspension, submitted in March 2026 and used in the pediatric program, would provide an option for patients who cannot swallow tablets.¹

Interpreting cenobamate PGTC data and next steps

The results add to evidence of broad-spectrum activity for cenobamate, but several caveats apply. Efficacy data are available so far only as sponsor-authored conference abstracts, not a peer-reviewed full publication.²,³ The placebo response was substantial, with roughly half of placebo recipients meeting the responder threshold.² Outcomes for the 34 adolescents were not reported separately, and a 12-week maintenance phase cannot speak to long-term seizure control, although the study includes an open-label extension.²,³ The company did not disclose FDA target action dates for either application.¹

References

1. SK Biopharmaceuticals submits supplemental new drug application to US FDA for cenobamate. News release. SK Life Science, Inc. November 4, 2026. Accessed November 4, 2026. https://www.prnewswire.com/news-releases/sk-biopharmaceuticals-submits-supplemental-new-drug-application-to-us-fda-for-cenobamate-302929394.html

2. Shih E, Bar M, Farkas M, Klein P, Vossler D, Misra S. Efficacy and safety of adjunctive cenobamate for the treatment of primary generalized tonic-clonic seizures in adults and adolescents. Abstract presented at: American Academy of Neurology Annual Meeting; 2026. Neurology. 2026. doi:10.1212/WNL.0000000000215694

3. Nisman A, Misra S, Ferrari L. Adjunctive cenobamate for the treatment of primary generalized tonic-clonic seizures in adults and adolescents: design of a phase 3 study with open-label extension. Abstract presented at: American Academy of Neurology Annual Meeting; 2025. Neurology. 2025. doi:10.1212/WNL.0000000000208535

4. Xcopri (cenobamate tablets). Prescribing information. SK Life Science, Inc.; 2024. Accessed November 4, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/212839s008lbl.pdf