Adolescent Cenobamate Exposure Aligns With Adults in New PK Modeling Analysis

Data presented at the 2026 American Academy of Neurology (AAN) Annual Meeting demonstrate that adolescents with focal epilepsy achieve cenobamate exposures comparable to adults, supporting the potential use of similar fixed-dose regimens in younger patients.¹

Cenobamate (XCOPRI), an antiseizure medication that enhances inhibitory signaling through GABAA receptor modulation while inhibiting persistent sodium currents, has become an important option for adults with focal seizures, particularly those with drug-resistant disease.² Its efficacy in reducing seizure frequency, along with emerging real-world and long-term safety data, has prompted increasing interest in extending its use to pediatric populations.

In the current analysis, investigators evaluated pharmacokinetic (PK) data from adolescents aged 12 to younger than 18 years enrolled in 2 open-label pediatric studies (C039 and C040), integrating these findings with adult PK data from prior trials.¹ Using population PK modeling, simulations were conducted to assess steady-state exposure following a 10-week titration and 10-week maintenance period across both weight-based and fixed-dose regimens.

Results showed that cenobamate PK in adolescents was adequately described by a two-compartment model with first-order absorption and elimination. Notably, adolescents receiving 4 mg/kg once daily achieved a mean steady-state exposure (AUC) of 510 µg•h/mL (90% prediction interval [PI], 251–883), while those receiving a fixed 200 mg dose reached 546 µg•h/mL (90% PI, 260–973).¹ These values were comparable to adult exposures at the approved 200 mg dose (434 µg•h/mL; 90% PI, 207–777), indicating pharmacokinetic alignment across age groups.¹

Across the full dosing range evaluated (100–400 mg daily equivalents), exposures remained consistent between adolescents and adults, suggesting that flat, fixed dosing strategies may be feasible without the need for strict weight-based adjustments.¹ This finding is particularly relevant for clinical practice, where simplified dosing regimens may improve adherence and ease of use, especially in adolescent populations transitioning to adult care models.

READ MORE: Phase 3 EPIC Trial to Evaluate NRTX-1001 Cell Therapy in Drug-Resistant Mesial Temporal Lobe Epilepsy

These PK findings are supported by a robust body of adult clinical data that established cenobamate’s role in epilepsy management. In pivotal randomized trials involving more than 600 patients with partial-onset seizures, cenobamate significantly reduced seizure frequency compared with placebo, with median reductions of 35.5%, 55.0%, and 55.0% at doses of 100 mg, 200 mg, and 400 mg, respectively, versus 24.0% with placebo.³ Importantly, up to 20% of treated patients achieved seizure freedom during maintenance phases, a notable outcome in a population with long-standing, refractory epilepsy.²

Beyond efficacy, safety optimization has also been a key focus in cenobamate development. Early concerns regarding drug reaction with eosinophilia and systemic symptoms (DRESS) led to implementation of slower titration schedules in later studies. In a large open-label trial of more than 1300 patients using gradual dose escalation, no cases of DRESS were reported, supporting the safety of current titration protocols.⁴

Additional regulatory updates have further expanded cenobamate’s clinical utility. In 2024, the FDA approved alternative administration methods, including crushed tablet delivery via oral suspension or nasogastric tube, based on pharmacokinetic studies demonstrating bioequivalence across administration routes.⁵ These options provide added flexibility for patients who have difficulty swallowing tablets or require alternative delivery methods in inpatient or institutional settings.

Taken together, the adolescent PK data presented at AAN 2026 extend the existing evidence base for cenobamate by demonstrating pharmacologic consistency across age groups. While efficacy and long-term safety data in pediatric populations remain to be fully established, these findings provide a critical step toward defining appropriate dosing strategies and support ongoing clinical development in younger patients with focal epilepsy.¹

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REFERENCES
1. Cenobamate in adolescent patients with focal epilepsy: a phase 1 pharmacokinetic study. Presented at: American Academy of Neurology Annual Meeting; April 18–22, 2026; Chicago, IL.
2. XCOPRI® (cenobamate tablets) CV Receives FDA Approval for Alternate Methods of Administration That Include Crushed Tablet in Liquid Suspension Taken Orally or Through a Nasogastric Tube. News Release. SK Life Science. Published April 11, 2024. Accessed April 23, 2026.
3. SK life science announces FDA acceptance of NDA submission for cenobamate, an investigational antiepileptic drug. News Release. SK Life Science. Published February 4, 2019. Accessed April 23, 2026. sklifescienceinc.com/pdf/SKLSI%20NDA%20Acceptance%20Press%20Release%20-FINAL-Updated%202-3-19.pdf.
4. Sperling M, Klein P, Kamin M. Safety of cenobamate (YKP3089) as an adjunctive treatment for uncontrolled partial seizures in a large, multi-center, open-label study. Presented at: American Epilepsy Society Annual Meeting; New Orleans, LA; December 2, 2018. aesnet.org/meetings_events/annual_meeting_abstracts/view/500991.
5. FDA Approves XCOPRI® (cenobamate tablets), an Anti-Epileptic Drug (AED) from SK Biopharmaceuticals, Co., Ltd., and U.S. Subsidiary SK Life Science, Inc. News Release. SK Life Science. Published November 21, 2019. Accessed April 23, 2026. https://www.sklifescienceinc.com/pdf/FDA_Approves_XCOPRI_(cenobamate_tablets)_an_Anti-Epileptic_Drug_(AED)_from_SK_Biopharmaceuticals_Co._Ltd._and_U.S._Subsidiary_SK_Life_Science_Inc.pdf