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THINK … EFFICACY, TOLERABILITY & LONG TERM

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Pubblished: 12/12/2024

5 minutes

Article

This webpage is intended for UK and Irish healthcare professionals. Prescribing information is available here.

Seizure Freedom is achievable in some patients: a data-driven look at the impact of adjunctive ONTOZRY®▼ (cenobamate), on Seizure Freedom rates in patients with focal epilepsy*

*Seizure freedom was a secondary endpoint of the pivotal phase II trial C017; the primary endpoint was seizure reduction.1

 

 

“I tried every medication that existed; however, nothing would minimise, let alone, stop the seizures”2

This statement highlights a common experience for doctors and their patients with epilepsy: the ongoing search for effective therapies that can provide lasting relief from seizures.  Finding the right treatment regimen often involves navigating a complex landscape of treatment options.2  

Cenobamate, an adjunctive treatment for focal-onset seizures in adults, offers a dual mechanism of action.15

Cenobamate is thought to potentially prevent seizure initiation and reduce seizure propagation through its action on 2 parts of the neurological signalling pathways involved in epilepsy.17 The precise mechanism of action by which Cenobamate exercises its therapeutic effects in patients with focal-onset seizures
is unknown.15

The following data deep dive will equip you with a better understanding of cenobamate's potential in achieving the "Think Seizure Freedom" goal for your patients. 

  • Cenobamate treatment has been associated with high seizure freedom rates.4  
    Efficacy of cenobamate was demonstrated in studies C013 and C017,  two randomized, double- blind, placebo-controlled, multicenter studies (treatment lengths ≤ 18 weeks) in adults with uncontrolled focal seizures despite taking 1–3 ASMs.5  


    Study C013 reported seizure freedom in 28.3% of participants administered 200 mg/day of cenobamate (vs 8.8% of those taking placebo)6; Study C017 demonstrate seizure freedom in 21% of participants taking 400 mg/day of cenobamate (vs 1% taking placebo).1

    Read more about Cenobamate efficacy data here.

  • The results observed in clinical trials are similar in real-world settings, with higher dosages† needed to achieve seizure freedom, particularly in the long term.3

    • A retrospective study conducted at two Italian epilepsy centers evaluated the effectiveness of cenobamate (CNB) as an add-on treatment in 54 adult patients (median age: 27.9 years) with drug-resistant focal epilepsy. All patients received CNB through Angelini Pharma's Early Access Program (EAP) between 2020 and 2022. Following CNB administration, a clinically meaningful reduction in seizure frequency was observed in most patients: 42.0% (n=20/54) experienced a >75% reduction in baseline seizure frequency, and 20.2% (n=10/54) achieved seizure freedom.4 
    • A multicentre, retrospective, observational study investigated real-world outcomes with adjunctive cenobamate in a large cohort of patients (n=170) with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). This study showed that 63% (n=104/165) of patients achieved a ≥50% reduction in seizure frequency​, and 13.3% (n=22/166) of patients were seizure-free at their last visit.3
    • A British Retrospective cohort study found that 59% (n= 84/142) of patients achieved a >50% reduction in seizure frequency at 6 months and 4.2% (n= 6/142) achieved seizure freedom at 6 months after receiving adjunctive cenobamate.10
    • Data from an early access program in Ireland further support the efficacy of adjunctive cenobamate and highlight the relationship between dosage and response. This single-center retrospective analysis of consecutive adults (n= 57) treated with cenobamate revealed that:
      • 42.1% of patients experienced a 75%–99% seizure frequency reduction (n=24/57);
      • 5.3% of patients achieved seizure freedom (n=3/57);
      • Adjunctive cenobamate led to abolition of Focal to bilateral tonic–clonic seizures (FBTCS) in over half of patients with active convulsions at baseline (63.2% of total patients): 55.6% of them had no further FBTCS on cenobamate (n=20/36).8 

     

  • High retention rates in long-term studies provide further evidence of adjunctive cenobamate's sustained efficacy and tolerability.7 

    • A post-hoc analysis observed high retention rates on adjunctive cenobamate during the clinical development program. An estimated 72% of patients remained on treatment at the end of 2 years (n=1309/1844). After titration, retention remained high, with cenobamate doses ≥100 mg/day†; concomitant anti-seizure medications did not impact retention.7 
    • In a Spanish Expanded Access Program (EAP) study, most patients continued to benefit from cenobamate and tolerated the treatment well over the course of a year, as demonstrated by the 87% retention rate at 12 months (n=40/46). 3

    • Real-world experience with cenobamate demonstrates that it is generally well tolerated by patients.
    • To date, more than 100,000 patients have been treated worldwide with cenobamate.10
    • AEs were frequent but mostly mild-to-moderate.3 In clinical trials C013, C017 and C021 the majority of adverse events were mild to moderate.  Most adverse events leading to study drug discontinuation in C013 and C017 occurred during titration, and adverse events were more frequent in patients receiving higher doses.11 

    • The titration schedule in the C017 study started at higher doses (50 mg or 100 mg once daily) and titrated rapidly (weekly or faster titration) compared to the recommended titration schedule. Due to the potential for serious adverse reactions, the recommended titration schedule should not be exceeded.​ C021 was designed to safely test whether starting at a lower dose and using a slower titration rate would lower the DRESS rates:​

      • Lower initial dose (12.5 mg/day, titrated gradually to target dose ​of 200 mg/day) and slower ​titration rate (2-week intervals up ​to 12 weeks)15​

      ​

    • The most commonly reported AEs in real-world studies were somnolence, dizziness, ataxia and diplopia.4,12,13   
    • In a British Retrospective cohort study 71% of patients (n=101/142) were able to reduce their dose and/or number of concomitant ASMs, which could help to reduce TEAEs.16

     

    Please refer to the full Summary of Product Characteristics (SmPC) before prescribing, particularly in relation to adverse reactions, precautions, contraindications and excipients.

     

UK: ONTOZRY®▼  is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled, despite treatment with at least 2 anti-epileptic medicinal products15

ROI: ONTOZRY®▼  is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least 2 anti-epileptic medicinal products15

 

† The recommended target dose of Cenobamate is 200 mg per day15

 

MAT-UKI-0148-P  February 2025

  1. Krauss GL et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol 2020; 19(1): 38-48.
  2. Reeder S, et al. Experience of waiting for seizure freedom and perception of machine learning technologies to support treatment decision: A qualitative study in adults with recent onset epilepsy.
    Epilepsy Res. 2023; 190:107096. 
  3. Villanueva V, et al. Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program. Epilepsia Open. 2023;8(3):918-929.
  4. Pietrafusa N, et al. Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence? Front Pharmacol. 2023 Dec 21;14:1239152. 
  5. Sperling MR,et al. Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open-label study. Epilepsia. 2021 Dec;62(12):3005-3015. 
  6. Chung SS, et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020 Jun 2;94(22):e2311-22.
  7. Sander JW, et al. Long‐term individual retention with cenobamate in adults with focal seizures: pooled data from the clinical development program. Epilepsia. 2022 Jan;63(1):139-49. 
  8. Peña-Ceballos J, et al. Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A “real-world” retrospective study. Epilepsia. 2023;64(5):1225-1235.
  9. Thomas R. From an early access program to real-word cenobamate In Angelini Pharma Satellite Symposium at ILAE 2023. Content Symposium Series 2023. 13(2):9-15 2023.
  10. Angelini Pharma UK-I, Data on file, UK2075NP
  11. Steinhoff BJ, et al. Practical guidance for the management of adults receiving adjunctive cenobamate for the treatment of focal epilepsy-expert opinion. Epilepsy Behav. 2021 Oct;123:108270. 
  12. Chen S, et al. Safety assessment of cenobamate: real-world adverse event analysis from the FAERS database. Frontiers in Pharmacology. 2024 Mar 15;15:1369384.
  13. Rodríguez‐Uranga JJ, et al. Treatment simplification to optimize cenobamate effectiveness and tolerability: A real‐world retrospective study in Spain. Epilepsia Open. 2024 May 27.
  14. Krauss GL, et al. Cognitive and psychiatric adverse events during adjunctive cenobamate treatment in phase 2 and phase 3 clinical studies. Epilepsy Behav. 2024 Feb;151:109605. 
  15. ONTOZRY® Summary of Product Characteristics. United Kingdom and European Union
  16. Aung P and Samarasekera S. Poster. ABN. 2024.
  17. Guignet M, et al. Epilepsia 2020;61:2329–39.

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