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C017 pivotal study: seizure frequency and seizure freedom

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The efficacy of adjunctive ONTOZRY® (cenobamate) in clinical trials

The efficacy of adjunctive ONTOZRY® for the treatment of uncontrolled focal onset epilepsy was evaluated in two multicentre, randomised, double-blind, placebo-controlled efficacy and safety studies and in one open-label safety study.1–3

ONTOZRY® (cenobamate) C017 pivotal study: seizure frequency and seizure freedom

C017 was a Phase IIb, multicentre, randomised, double-blind, placebo-controlled, dose-response study with an optional open-label extension (OLE).1

Reducing seizure frequency with adjunctive ONTOZRY® (cenobamate): primary endpoints

The two primary endpoints of C017 were:1

  • % of patients achieving ≥50% reduction from baseline in focal seizure frequency (during the 12-week maintenance phase of the double-blind period) when adding placebo or ONTOZRY® to an ongoing regimen of 1-3 anti-seizure medications (ASMs) (Standard of care; SoC)*.
  • % change from baseline in focal seizure frequency averaged over 28 days in the 18-week double blind treatment period.

Adjunctive ONTOZRY® reduces the frequency of drug-resistant focal onset seizures by ≥50% in over half of patients.1

C017 primary endpoint results graph titled % of patients with ≥50% reduction in seizure frequency (measured over a 12-week maintenance phase) when placebo or ONTOZRY® was added to an ongoing regimen of 1-3 ASMs (SoC). The % of total patients achieving ≥50% reduction is shown on the y-axis and the fourtreatment groups are displayed on the x-axis: SoC + Placebo (25.5%), SoC + ONTOZRY® 100 mg (40.2%), SoC + ONTOZRY® 200 mg(56.1%), and SoC + ONTOZRY® 400 mg (64.2%).

*SoC was treatment with up to three concomitant anti-seizure medications.1

ONTOZRY® (cenobamate) and seizure freedom: secondary endpoints

The key secondary endpoints of C017 were:1

  • % of patients with ≥75%, ≥90% and 100% reduction in seizure frequency (measured over a 12-week maintenance phase) when adding placebo or ONTOZRY® to SoC.
  • % change from baseline in seizure frequency per 28 days by seizure type (measured over a 12-week maintenance phase) when placebo or ONTOZRY® was added to SoC.

Seizure freedom is possible with adjunctive ONTOZRY® for some drug-resistant patients†1

C017 secondary endpoint diagram showcasing the percentage of patients in two treatment groups ( ONTOZRY® 400 mg/day and ONTOZRY® 200 mg/day) who achieved 100% reduction in seizure frequency (measured over a 12-week maintenance phase) when adding placebo or ONTOZRY® to SoC.

Adjunctive ONTOZRY® is associated with dose-dependent improvements in ≥75%, ≥90% and 100% responder rates.1

Three C017 secondary endpoint graphs illustrating dose-dependent improvements in ≥75%, ≥90%, and 100% responder rates. The y-axis represents the percentage of patients reaching each responder rate; the x-axis lists the responder rate categories. Each individual chart compares four treatment groups: SoC + Placebo, SoC + ONTOZRY® 100 mg, SoC + ONTOZRY® 200 mg, and SoC + ONTOZRY® 400 mg.

Adjunctive ONTOZRY® reduces seizure frequency in patients with epilepsy with different focal seizure subtypes.1

†When added to standard of care (an ongoing regimen of 1-3 ASMs).

Abbreviations

ASM, anti-seizure medication; EMA, european medicines agency; FDA, food and drug administration; ILAE, international league against epilepsy; OLE, open-label extension; SoC, standard of care.

  1. Krauss GL, Klein P, Brandt C, 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. The Lancet Neurology. 2020;19(1):38-48. doi:https://doi.org/10.1016/s1474-4422(19)30399-0
  2. Chung SS, French JA, Kowalski J, et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020;94(22):e2311-e2322. doi:https://doi.org/10.1212/wnl.0000000000009530
  3. Sperling MR, Klein P, Aboumatar S, et al. Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open‐label safety study. Epilepsia. 2020;61(6):1099-1108. doi:https://doi.org/10.1111/epi.16525
  4. Klein P, Aboumatar S, Brandt C, et al. Long-term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures. Neurology. 2022;99(10):e989-e998. doi:https://doi.org/10.1212/WNL.0000000000200792
  5. Sander JW, Rosenfeld WE, Halford JJ, Steinhoff BJ, Biton V, Toledo M. Long‐term individual retention with cenobamate in adults with focal seizures: Pooled data from the clinical development program. Epilepsia. 2021;63(1):139-149. doi:https://doi.org/10.1111/epi.17134
  6. Rosenfeld WE, Abou‐Khalil B, Aboumatar S, et al. Post hoc analysis of a phase 3, multicenter, open‐label study of cenobamate for treatment of uncontrolled focal seizures: Effects of dose adjustments of concomitant antiseizure medications. Epilepsia. 2021;62(12):3016-3028. doi:https://doi.org/10.1111/epi.17092
  7. Sperling MR, Abou‐Khalil B, Aboumatar S, et al. Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open‐label study. Epilepsia. 2021;62(12):3005-3015. doi:https://doi.org/10.1111/epi.17091

MAT-UKI-0451-P | June 2026