Cenobamate: A Shift to Earlier Therapy

Despite over 25 years of advancements in anti-seizure medications (ASMs), over 35% of patients continue to experience uncontrolled seizures2, and the probability of achieving seizure freedom diminishes substantially with each subsequent ASM regimen tried.3 This highlights the urgent need to revitalize the development of ASMs to discover more effective drugs for the treatment of drug-resistant epilepsy.⁴

Ontozry (cenobamate, CNB) an ASM often reserved as a later-line option, is now being investigated for its potential benefits when utilized earlier in the treatment course. This shift in strategy is supported by recent research, including findings presented at the EEC-ILAE 2023 Congress, since published by Winter and colleagues in CNS Drugs (2024).⁵
   
Winter et al. presented a unicentric observational study of 231 drug-resistant epilepsy (DRE) patients, specifically examining CNB (n=77) as an early adjunctive therapy. The study focused on patients who had failed two or three prior ASMs. Patients were matched (1:2)  by sex, age, and types and frequency of seizures to a comparator group who did not respond to two or three prior ASMs and initiated with any other adjunctive ASM. The comparator group (n=154) included lacosamide, LCS (n=40), levetiracetam, LEV (n=38), topiramate, TPM (n=32), and valproate, VPA (n=44).⁵

Cenobamate as early add-on therapy vs. other ASMs: new data for clinical practice

Winter's study revealed several key findings that highlight the potential of early CNB intervention:

• Significant retention rate
  The highest 12-months retention rate was observed on CNB (92.0%, compared with all other ASMs), followed by LCS (80.0%), LEV (73.3%), VPA (68.2%), and TPM (62.5%).⁵
• Significant responder rate
  CNB showed the highest responder rate (≥ 50% reduction of seizures) of 71% for all types of seizures compared with other groups of ASM (VPA 55 %, LCS 53%, LEV 53%, and TPM 50%).⁵
• Significant seizure freedom
  Seizure freedom was achieved by 20% of patients on CNB, which was higher than in patients on LCS (8%), LEV (8%), and TPM (6%).⁵
• Efficacy in FBTCS
  The highest efficacy of CNB was observed in focal-to-bilateral tonic-clonic seizures (FBTCS) with a responder rate (≥ 50% reduction of seizures) of 73% and seizure freedom of 20%, which were significantly higher compared with all other groups of ASMs (LEV 55% and 9%, LCS 54% and 8%, TPM 52% and 12% and VPA 50% and 6%).⁵

Cenobamate efficacy shown as an early adjunctive therapy for focal-onset seizures

Although randomized controlled trials are an essential steppingstone in establishing the safety and efficacy of drugs, shorter time frames and inflexible dosage regimens provide results that sometimes may not be easily extrapolated to the everyday clinical setting. The study from Winter et al. above showcases retention rate data from patients who received CNB early on in treatment within a real-life clinical context, where patients were given the therapy as early as permitted by authorization criteria. The significant retention rates demonstrated for CNB therapy (92%) compared with control ASMs in the cohort give an indication that the results seen in cenobamate clinical trials may be confirmed in real-life clinical setting. This may give further support for clinical decision making in the management of patients with refractory seizures and support the use of Ontozry in earlier therapy lines for these patients.⁵

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Ontozry® (cenobamat) 12,5 mg odragerad tablett samt 25 mg, 50 mg, 100 mg, 150 mg och 200 mg filmdragerade tabletter. Rx F. ATC-kod: N03AX25 - antiepileptika, övriga antiepileptika. Indikation: Ontozry är indicerat som tilläggsbehandling av fokala anfall, med eller utan sekundär generalisering hos vuxna patienter med epilepsi, som inte kontrollerats tillräckligt trots tidigare behandling med minst två antiepileptika. Kontraindikationer: Överkänslighet mot den aktiva substansen eller mot något hjälpämne, ärftligt kort QT-syndrom. Varningar: Patienter ska instrueras att uppsöka läkare om tecken på självmordstankar/självmordsbeteende uppstår, samt om tecken och symptom på läkemedelsreaktion med eosinofili och systemiska symtom (DRESS) inträffar. Innehåller laktos. Cenobamat kan minska exponeringen av substanser som metaboliseras via CYP3A4, CYP2B6 samt öka exponeringen av substanser som metaboliseras via CYP2C19. Cenobamat rekommenderas inte till fertila kvinnor som inte använder preventivmedel eller vid amning. MAH: Angelini Pharma S.p.A. Lokal kontakt: Angelini Pharma Nordics, nordic.medinfo@angelinipharma.com. Datum för senaste översyn av SPC: 9/2025. För pris och ytterligare information, se www.fass.se.