During months 36 and 48 on open-label cenobamate treatment, 76.4% and 51.8% of patients achieved seizure reductions of at least 50% or 75%, respectively.
Newly published data from the long-term, open-label extension (OLE) of the randomized, placebo-controlled C017 study (NCT01866111) of cenobamate (Xcopri; SK Life Sciences) showed that the antiseizure medication sustained efficacy after 48 months, with more than 15% of patients achieving 100% seizure freedom.1,2
Approved in 2019 to treat partial-onset seizures, cenobamate was evaluated in a cohort of 355 patients, aged 18 to 70 years, with uncontrolled focal seizures who completed the 18-week double-blind study. At months 12, 24, 36, and 48, a total of 83%, 71%, 65%, and 62% of patients were retained on cenobamate treatment. Despite failing 1 to 3 previous antiseizure medications, 16.4% (36 of 220) and 39.1% (86 of 220) achieved 100% or at least 90% seizure reduction, respectively, during months 36 through 48.
"We were pleased to see these results in such a difficult to treat patient population," Pavel Klein, MD, epileptologist and neurologist, Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Maryland, said in a statement.1 "More than three-quarters of patients treated with cenobamate experienced a reduction in seizure frequency of 50% or more during years 3 to 4 of the study. Physicians may want to consider whether patients with partial-onset (focal) seizures are appropriate candidates for adjunctive treatment with cenobamate."
Patients who chose to enter the OLE underwent a 2-week double-blind conversion to a target dose of cenobamate 300 mg once daily. For those originally assigned to placebo in the double-blind study, open-label treatment with cenobamate started at a target dose of 100 mg/day at week 1, followed by 200 mg/day at week 2, and 300 mg/day starting at week 3. During the OLE treatment phase, concomitant antiseizure medications (ASMs) could be added, removed, or adjusted, with cenobamate dose adjusted as well, if needed.
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As of July 2019, 58.9% (209 of 355) of patients were continuing in the OLE, with 16.6% discontinuing because of lack of efficacy, 8.7% because of withdrawal by patient, and 7.6% because of adverse events (AEs). During the first 6 months of the OLE, investigators observed a median percent reduction of 65.4% (interquartile range [IQR], 52%) for all individuals on cenobamate, regardless of previous treatment with placebo. With each 6-month OLE interval, the median percent reduction continued to increase, up to 76.1% at months 43 to 48.
When using the original modified intent-to-treat population (n = 354) as the denominator, 10.2% of patients achieved 100% seizure reduction during the last 12 months of the 48-month treatment phase. Additionally, any consecutive duration of seizure freedom lasting at least 12 or 24 months was observed in 18.4% and 11.9% of individuals, respectively. During months 36 and 48, 76.4% of patients had seizure reductions of at least 50% and 51.8% showed reductions of at least 75%.
Pneumonia/sepsis, septicemia, fatal injuries after being struck by car, cardiogenic shock, myocardial infarction, and suicide, accounted for the 6 deaths observed in the OLE, all of which were unrelated to cenobamate. Serious treatment-related AEs occurred in 20.3% of those in the OLE, the most common being seizure (1.4%), vertigo (1.1%), and seizure cluster (0.8%), followed by several others. Serious treatment-emergent AEs considered to be related to cenobamate occurred in 5.4% of patients.
In total, 31 patients (8.7%) had at least 1 treatment-emergent AE that led to discontinuation, most frequently because of nervous system disorders (3.4%), dizziness (0.8%), somnolence (0.6%), balance disorder (0.6%), and depression (0.6%). Psychiatric disorders leading to discontinuation were reported in 6 patients (1.7%), including depression in 2 patients, and bradyphrenia, hallucination, persistent depressive disorder, and psychotic disorder in 1 patient each.