FDA Approves Cenobamate for Treatment of Partial-Onset Seizures in Adults

The Food and Drug Administration has approved cenobamate (Xcopri; SK Life Sciences, Paramus, NJ) for the treatment of partial-onset seizures in adults. 

Approval was based on 2 randomized double-blind placebo-controlled studies that enrolled 655 adults with partial-onset seizures with or without secondary generalization. Participants had mean disease duration of 24 years and median seizure frequency of 8.5 seizures per 28 days during an 8-week baseline period. During the trials, doses of 100, 200, and 400 milligrams (mg) daily of cenobamate reduced the percent of seizures per 28 days compared with the placebo group. The recommended maintenance dose of cenobamate, following a titration (medication adjustment) period, is 200 mg daily. Some individuals may need additional titration to 400 mg daily, the maximum recommended dose.

In a phase 2 trial (NCT01866111) treatment with cenobamate 100 mg, 200 mg, and 400 mg had median seizure frequency reduction of 36%, 55%, and 55%, respectively vs 24% with placebo. Those doses also resulted in a 50% or more reduction in focal seizures compared with baseline during the maintenance phase (40%, 56%, and 64%) vs placebo (25%). During the maintenance phase, 4%, 11%, and 21% of participants treated with cenobamate 100 mg, 200 mg, and 400 mg reported no focal seizures compared with only 1% of placebo-treated participants. 

Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research said, “Xcopri is a new option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life. Patients can have different responses to the various seizure medicines that are available. This approval provides an additional needed treatment option for people with this condition.

As quoted previously in Practical Neurology, Marc Kamin, MD, chief medical officer, SK Life Science said, "More than one-third of patients with epilepsy have uncontrolled seizures and treatment outcomes for these patients have not substantially improved over the past 20 years." Based on the results in the maintenance phase of the study, a post-hoc analysis of the number of patients needed to treat to get someone to 0 focal seizures was 10 for the 200 mg dose and 5 for the 400 mg dose. We are encouraged by these results as they suggest that cenobamate may be able to help patients with focal seizures who have not yet achieved adequate seizure control." 

The most common side effects that patients in the clinical trials reported were somnolence (sleepiness), dizziness, fatigue, diplopia (double vision), and headaches. People taking cenobamate should be advised not to drive until they know how the medication effects them. 

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported among patients taking cenobamate during clinical trials, and 1 participant died when cenobamate was titrated rapidly (weekly or faster titration). However, there were no cases of DRESS in an open-label safety study of 1,339 people with epilepsy when cenobamate was started at 12.5 mg/day and adjusted every 2 weeks. A higher percentage of people taking cenobamate vs placebo had a shortening of the QT interval more than 20 msec. Cenobamate should not be used in those with hypersensitivity to cenobamate or with familial short QT syndrome. Antiseizure medications (ASMs), including cenobamate, increase risk of suicidal indeation, and people taking any ASM  should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.