Cenobamate Data Shows Seizure Reduction, Lower Health Care Use, and Potential SUDEP Risk Reduction

Vicente Villanueva, MD, PhD

(Credit: Dravet Syndrome Foundation)

Angelini Pharma presented new data at the 36th International Epilepsy Conference (IEC), held August 31 to September 3, 2025, in Lisbon, Portugal, showing that treatment with antiseizure medication (ASM) cenobamate (Ontozry) in adults with uncontrolled focal onset seizures led to benefits beyond seizure control, including decreases in hospitalizations and emergency department visits as well as reductions in sudden unexpected death in epilepsy (SUDEP).¹

Cenobamate is approved in Europe as an add-on treatment for focal-onset seizures, with or without secondary generalization, in adults whose epilepsy remains uncontrolled after treatment with at least 2 ASMs.² A retrospective analysis of a Spanish cohort from a multicenter, phase 3, open-label study (NCT02535091) conducted across 9 hospitals and involving 129 patients reported substantial reductions in seizure frequency, along with high and sustained rates of seizure freedom.

In the presented analysis, cumulative retention rates were 71%, 60%, and 56% at 1 year, 2 years, and 3 years, respectively. At the final visit, 28.7%, 18.8%, and 11.8% of patients had remained seizure-free for at least 1 year, 2 years, and 3 years, respectively.³ Seizure freedom rates were higher among those who had previously failed 3 or fewer ASMs, underscoring the potential benefit of initiating treatment with effective therapies earlier in the disease course.⁴

"Access to and early use of the latest ASMs can significantly transform the patient experience for people living with epilepsy," Vicente Villanueva, MD, PhD, Head of Section, Associate Professor of Neurology, Refractory Epilepsy Unit, Neurology Service Hospital Univesitario y Politecnico La Fe, Spain, said in a statement.¹ "ASMs are critical in achieving the long-term objective of epilepsy care and management-seizure freedom and its subsequent benefits"

READ MORE: Praxis’ Vormatrigine Shows Significant Ability to Reduce Seizure Incidence in Phase 2 RADIANT Study

A post-hoc analysis of this cohort presented at IEC 2025 showed that patients who maintained seizure freedom, particularly freedom from focal to bilateral tonic-clonic seizures, had a statistically significant reduction in the risk of SUDEP, as measured by the validated SUDEP-3 and SUDEP-7 scales.⁵ The company noted that these results highlighted the association between sustained seizure freedom and reduced SUDEP risk, suggesting that this potential benefit may be relevant when initiating or adjusting treatment in patients with uncontrolled focal seizures.

In a retrospective observational study using the IQVIA PharMetrics Plus database, researchers examined healthcare utilization among adults with focal-onset seizures treated with cenobamate in the United States. Presented at IEC 2025, the analysis showed a reduction in the proportion of patients requiring hospitalization or emergency department visits, indicating potential benefits beyond seizure control and suggesting a possible impact on health care resource use.⁶

A separate study presented at IEC 2025 using an artificial intelligence (AI) and machine learning (ML)–based analysis explored the bidirectional relationship between epilepsy and depression. Overall, the study helped identify key risk factors for depression in individuals with epilepsy, and for epilepsy in those with depression, offering potential insight into opportunities for earlier, targeted interventions.⁷

"Researching new ways to allow patients to achieve seizure control is our focus at Angelini Pharma," Rafal Kaminski, chief scientific officer at Angelini Pharma, said in a statement.¹ "Epilepsy affects an estimated 50 million people worldwide, and our mission is to develop innovative solutions that help individuals with uncontrolled seizures take control of their condition, with the ultimate goal of achieving seizure freedom."

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REFERENCES
1. Angelini Pharma Presents Data Demonstrating Benefits of Cenobamate for Adults Living with Uncontrolled Epilepsy. News Release. Angelini Pharma. Published September 1, 2025. Accessed September 8, 2025. https://www.publicnow.com/view/65F91197B831258D37B27E84A30A9A6C7F653F43?1756712840
2. ONTOZRY® (Cenobamate) Receives European Commission Approval for the Treatment of Drug-Resistant Focal-Onset Seizures in Adults. News Release. SK Biopharmaceuticals. Published March 30, 2012. Accessed September 8, 2025. https://www.sklifescienceinc.com/pdf/ONTOZRY_Receives_European_Commission_Approval.pdf
3. Serratosa et al. Efficacy and safety of cenobamate in adults with uncontrolled focal seizures in the Spanish cohort of a Phase 3 open-label clinical trial: a multicenter retrospective study. Presented at: 36th International Epilepsy Conference (IEC); August 31 to September 3, 2025, in Lisbon, Portugal.
4. Lattanzi S. et al. Effectiveness and safety of adjunctive cenobamate in people with focal-onset epilepsy: Interim results after 24-week observational period from the BLESS study. Epilepsia. 2025 Jul;66(7):2239-2252. doi: 10.1111/epi.18357. Epub 2025 Mar 15. August 2025
5. Villanueva et al. Effect of cenobamate on sudden unexpected death in epilepsy (SUDEP) risk in a Spanish cohort of a phase 3 clinical trial. Presented at: 36th International Epilepsy Conference (IEC); August 31 to September 3, 2025, in Lisbon, Portugal.
6. Lovera et al. Healthcare Resource Utilization among Adult Patients with Focal-Onset Seizures using Cenobamate: a US Database Analysis. Presented at: 36th International Epilepsy Conference (IEC); August 31 to September 3, 2025, in Lisbon, Portugal.
7. Ruggieri et al. Exploring the epilepsy-depression relationship using Artificial Intelligence on Real-World Data in Germany, France, Italy and Spain. Presented at: 36th International Epilepsy Conference (IEC); August 31 to September 3, 2025, in Lisbon, Portugal.