Cenobamate Safe, Effective Over Long-Term Treatment

December 9, 2019

Adjunctive cenobamate demonstrated a good tolerability and safety profile, as well as sustained efficacy, in patients with uncontrolled focal seizures.

Jacqueline A. French, MD

Results of interim analyses of 2 open-label extension studies of adjunctive cenobamate (SK Life Science) confirm the drug’s safe and tolerable profile as well as its sustained efficacy across long-term treatment in patients with uncontrolled focal seizures. The data were presented at the 2019 American Epilepsy Society Annual Meeting, December 6-10, 2019 in Baltimore, Maryland.1,2

The FDA recently approved cenobamate for the treatment of partial-onset seizures in adults. The drug is expected to become available in the US in the second quarter of 2020 following scheduling review by the Drug Enforcement Administration.

Long-term safety data were collected from the ongoing open-label extension study of the phase 2, 12-week, double-blind, placebo-controlled trial (NCT01397968).1

Patients included in the original trial were between the ages of 18 and 65, had uncontrolled seizures, had at ³3 seizures per month and were on stable doses of 1 to 3 antiepileptic drugs (AEDs). Participants who were eligible for the trial were randomly assigned to 200 mg/d of cenobamate or placebo. Upon completion, patients became eligible for the open-label extension study.

Ultimately, 149 patients entered the open-label study, 76 of whom were originally randomized to cenobamate and 73 who were randomized to placebo and who transitioned to cenobamate. The participants were in on a median of 2 AEDs and received a median modal daily dose of cenobamate 200 mg (range, 50-400 mg), with a median exposure duration of 60.6 months (range, 0.3-79.4 months).

Ultimately, there were 132 (88.6%) instances of treatment-emergent adverse events (TEAEs) combined in both groups. Dizziness was the most common TEAE, reported among 48 (32.2%) patients, There were 34 instances of serious TEAEs, 22 of which were reported in the cenobamate group and 12 reported in the placebo/ cenobamate group, and included seizure, pneumonia, sepsis, and osteoarthritis.

As of April 2018, 86 (57.7%) patients remained in the study, 40 (52.6%) of whom received cenobamate and 46 (63%) in the placebo/ cenobamate group. Reasons for discontinuation were withdrawal by patient, adverse events, lost to follow-up, pregnancy, and other.

Additionally, investigators reported efficacy results from the open-label extension of the phase 2, double-blind, randomized, placebo-controlled dose response study (NCT01866111) that included data from 355 patients, 265 of whom were originally randomized to receive cenobamate and 90 who received placebo and transitioned to the study drug with a median exposure duration of 40.1 months to a median dose of 300 mg/d cenobamate.2 As of April 2018, 64.8% of patients remained, with discontinuations due to lack of efficacy (15.5%), adverse events (6.8%), patient withdrawal (6.5%), or other (6.5%).

In the intent-to-treat population (n=354), a median 65.4% reduction in seizure frequency was recorded in the first 6 months of the extension study. Reduction in frequency increased with study duration, with a median 76% reduction recorded at 25 to 30 months, with 20.2% of patients achieving seizure freedom during that time period.

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REFERENCES

1. French JA, Chung SS, Krauss GL, et al. Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: open-label extension of a randomized clinical study. Presented at: 2019 American Epilepsy Society Annual Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 3.297.

2. Klein P, Krauss GL, Aboumatar S, Kamin M. Long-term efficacy and safety of adjunctive cenobamate in patients with uncontrolled focal seizures: open-label extension of a randomized clinical study. Presented at: 2019 American Epilepsy Society Annual Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 2.206.