Angelini Pharma Presents Data Demonstrating Benefits of Cenobamate▼ for Adults Living with Uncontrolled Epilepsy

• Findings from a post-hoc analysis of the phase 3 open label clinical trial demonstrated that cenobamate sustained seizure freedom, specifically freedom from focal to bilateral tonic-clonic seizures, led to a reduction in the risk of sudden unexpected death in epilepsy (SUDEP).
• Additionally, results from a US database analysis looking at adults with focal onset seizures treated with the product demonstrated a significant reduction of all-cause hospitalization and emergency department visits 6 months after treatment initiation compared to baseline.

Rome (Italy) [09, 01, 2025] - Angelini Pharma, part of the privately owned Angelini Industries, shared positive findings from clinical trials and real world clinical practice in adults living with epilepsy and uncontrolled focal onset seizures, demonstrating that treatment with cenobamate provided benefits beyond seizure reduction, leading to a decrease in hospitalizations and emergency department visits, alongside data demonstrating the potential to reduce SUDEP. These results were presented as part of the 36^th International Epilepsy Conference (IEC) in Lisbon, Portugal, from 31 August to 3 September 2025.

Cenobamate is an anti-seizure medication (ASM) approved in Europe as adjunctive treatment of focal-onset seizures with or without secondary generalization in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-seizure medications.¹

The retrospective study including the Spanish cohort of the multicenter phase 3 open label study, conducted across nine Spanish hospitals and involving 129 patients, demonstrated a high reduction in seizure frequency including high and maintained seizure freedom rates. Cumulative retention rates were 71%, 60% and 56% at 1, 2 and 3 years respectively. At the last visit, 28.7%, 18.8% and 11.8% of the patients were continuously seizure free for at least 1 year, 2 years, and 3 years respectively.² Seizure freedom rates were higher in people who previously failed 3 or less ASMs, highlighting the importance of early treatment with efficacious drugs.³

A post-hoc analysis of this population showed that patients who maintained seizure freedom, specifically freedom of focal to bilateral tonic-clonic seizures, also had a statistically significant reduction of the risk of sudden unexpected death, as measured by validated scales SUDEP-3 and SUDEP-7.⁴ These findings are crucial, highlighting the importance of achieving seizure freedom and cenobamate's role in improving patient life and the importance of considering the potential for reducing SUDEP risk when initiating and/or changing treatment in patients with uncontrolled focal seizures.

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

Additionally, a retrospective observational study of IQVIA PharMetrics Plus database analysing healthcare utilization among adult patients with focal-onset seizures treated with cenobamate in the U.S., revealed a notable reduction in the percentage of people requiring hospitalization and emergency room visits.⁵ The observed significant drop in hospitalization rates and emergency department visits not only reflects improved clinical outcomes beyond seizures but also underscores cenobamate's potential to reduce healthcare costs and improve quality of life.

Angelini Pharma also introduced research employing AI models to better understand the bidirectional relationship between epilepsy and depression. This cutting-edge study using Artificial Intelligence and Machine Learning identified critical risk factors for depression in people with epilepsy and vice-versa, providing a pathway for targeted early interventions.⁶ This research supports a holistic approach to brain health care, ultimately improving quality of life for individuals with epilepsy and depression.

"Researching new ways to allow patients to achieve seizure control is our focus at Angelini Pharma," said Rafal Kaminski, Chief Scientific Officer, Angelini Pharma. "Epilepsy affects an estimated 50 million people worldwide⁷, 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."

▼This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 of the package leaflet for how to report side effects.

About Epilepsy

Epilepsy is one of the most widespread neurological diseases in the world, affecting globally approximately 50 million people of all ages.⁵ In Europe, up to six million people are estimated to be living with this disease.⁸ Epilepsy can have multiple potential causes, including structural, metabolic, genetic and other factors, though approximately half of cases worldwide do not have a known cause.⁵

The complications associated with epilepsy are severe, with a risk of premature mortality up to three times higher than the general population. The recurrent seizures associated with this condition also have wide-ranging effects on a person's broader physical and mental health, education and employment opportunities and other quality of life factors.⁵

Treatments are available to help reduce seizures and improve quality of life, however approximately 40% of people living with epilepsy are still uncontrolled despite the treatment with two ASMs.⁹

About the Phase 3 Open-Label Extension Study published in Epilepsia

NCT02535091 (C021, N=1340) was a global prospective, multicenter, phase 3, open-label safety study of cenobamate as adjunctive treatment in adults with uncontrolled focal-onset seizures (FOS) taking 1-3 ASMs at baseline. The mean (SD) age was 39.7 (±12.8) years, 49.7% of patients were female, the mean (SD) epilepsy duration was 22.9 (±14.4) years, the majority of patients were white (79.4%), and 43.5% were taking 3 or more concomitant ASMs at baseline.¹⁰

About abstract P1075: the retrospective efficacy and safety study on the Spanish population of the Phase 3 Open-Label Extension Study

This was a multicenter, retrospective, observational study in 9 Spanish hospitals, including 129 patients. The primary endpoint was retention rate; secondary endpoints included reductions (100%, ≥90%, ≥75%, ≥50%) in seizure frequency, concomitant ASM management, and safety.²

About abstract P021: IQVIA AI study on links to depression

This study extends the analysis of depression predictors in patients with epilepsy (PWE) to additional countries (France, Italy and Spain) and explores predictors of epilepsy in patients with depression (PWD) through Machine Learning (ML) to identify predictors of depression in PWE. Country-specific tree-based models were trained to predict risk of depression onset in PWE and epilepsy onset in PWD using EMR and prescription data. Recorded diagnoses, prescriptions and visits were used as input features. Explainable AI identified important features for prediction.

About abstract P636: IQVIA retrospective healthcare resource study

This retrospective observational study utilized the IQVIA PharMetrics Plus database, containing medical claims of approximately 140 million US enrollees. Adult cenobamate users with FOS were identified with the first cenobamate dispensation as index date (indexing period: April 1, 2020, to April 30, 2023). Eligible patients were required to have a pre-index 6-month baseline period, and 6-month follow-up. A treatment regimen evaluation (TRE) window of 90 days post-index was defined to evaluate patients on monotherapy (≥90 days prescription claims), polytherapy (overlapping ≥90 days' supply of cenobamate and at least one ASM within +/- 30 days from cenobamate dispensing) or undetermined (all others). HCRU parameters of pre-index vs. follow-up were compared.⁵

About ONTOZRY^® (cenobamate▼)

The product is an anti-seizure medication (ASM) approved in Europe as adjunctive treatment of focal-onset seizures with or without secondary generalization in adult patients living with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medicinal products.¹

The product is a novel small molecule that provides a dual, complementary mechanism of action aimed at reducing seizures. The dual mechanism of action suggests that it has the potential to both prevent seizure initiation and limit seizure spread.^11,12The precise mechanism of action by which cenobamate exercises its therapeutic effects in patients with focal-onset seizures is unknown.

Cenobamate was discovered and developed by SK Biopharmaceuticals and its U.S. subsidiary SK Life Science.

Long-term data on the product was studied in open-label extensions of the double-blind placebo-controlled trials, as well as the open-label safety studies in adults with uncontrolled focal-onset seizures. Additionally, cenobamate was assessed in a randomized, double-blind, placebo-controlled trial evaluating its safety and efficacy as adjunctive therapy in patients with primary generalized tonic-clonic seizures (NCT03678753).^{13,14,15,16,17}

1. Ontozry Summary of Product Characteristics. European Medicines Agency. Available at: https://www.ema.europa.eu/en/documents/product-information/ontozry-epar-product-information_en.pdf. Accessed August 2025.
2. 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 2025
3. 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
4. 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 2025
5. 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 2025
6. 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 2025
7. World Health Organisation. "Epilepsy Key Facts." Available at: https://www.who.int/en/news-room/fact-sheets/detail/epilepsy. Accessed August 2025.
8. Behr et al. Epidemiology of epilepsy. Revue Neurologique 2016 Jan; 172(1):27-36. doi: .1016/j.neurol.2015.11.003
9. Chen Z, Brodie MJ, Liew D, Kwan P. Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neurol. 2018 Mar 1;75(3):279-286. doi: 10.1001/jamaneurol.2017.3949. Erratum in: JAMA Neurol. 2018 Mar 1;75(3):384. doi: 10.1001/jamaneurol.2018.0018. PMID: 29279892; PMCID: PMC5885858.
10. Sperling MR, et al. Safety of cenobamate (YKP3089) as adjunctive treatment for uncontrolled partial (focal) seizures: results from a large, phase 3, multicenter, open-label study. Presented at: American Epilepsy Society Annual Meeting; November 30-December 4, 2018; New Orleans, LA. Abstract 1.303 and encored at the American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA. Available at: https://onlinelibrary.wiley.com/doi/10.1111/epi.16525 . Accessed August 2025.
11. Guignet et al. Epilepsia 2020;61:2329-39
12. Löscher et al. Epilepsia 2021;62:596-614
13. French et al. Epilepsia 2021;62:2142-50
14. Klein et al. Neurology 2022, 99 (10) e989-e998
15. Chung et al. Neurology 2020;94:e2311-e22
16. Krauss et al. Lancet Neurol 2020;19:38-48
17. Sperling et al. Epilepsia 2020;61:1099-108