Results from a randomized placebo-controlled study published in Neurology show that cenobamate (Xcopri; SK Life Science, Paramus, NJ) significantly reduced seizure frequency in adults with uncontrolled partial-onset (focal) seizures Cenobamate is now available for prescription after having been approved by the Food and Drug Administration (FDA) in Nov 2019.
The key findings include a greater median percent seizure reduction with the therapy (56%) compared with placebo (22%). Also, more participants who were given the therapy achieved a 50% or more reduction in seizure frequency (50%) compared with those in the placebo group (22%).
The randomized, placebo-controlled study evaluated the safety and efficacy of the drug given at 200 mg/day as an adjunctive therapy in adults 18 to 65 years of age with uncontrolled focal seizures. In the study, 222 participants were randomized (113 received the therapy and 109 received placebo) in a 12-week, double-blind treatment period that included a 6-week titration phase and a 6-week maintenance phase.
Also, post hoc analyses of the maintenance phase showed that greater percentages of participants taking the therapy vs placebo achieved seizure reduction rates of ≥75% (39% with the therapy vs 21% with placebo) ≥ 90% (34% with the therapy vs 9% with placebo) and 100% or 0 seizures (28% with the therapy vs 9% with placebo).
“A substantial number of patients continue to deal with the impact of ongoing seizures, even as many new ASMs have become available over the last 25 years,” said Steve S. Chung, MD, executive director, Neuroscience Institute; and director, Epilepsy Program, Banner–University Medical Center. “We are encouraged by the results of this study, as patients taking cenobamate saw significant reductions in seizure frequency—with 28% of patients reaching 0 seizures during the maintenance phase.”
In a long-term, open-label safety study published in Epilepsia, 83% of participants continued cenobamate treatment for 6 months or more with no new safety signals. In this study, 1,339 participants who were taking 1 to 3 other antiseizure medications and had a starting dose of 12.5 mg/day of cenobamate that was titrated up as needed (by 50 mg every 2 weeks), no cases of drug reaction with eosinophilia and systemic symptoms (DRESS) were seen.
Although the precise mechanism by which the drug exerts its therapeutic effect is unknown, it is believed to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. It is also a positive allosteric modulator of the γ-aminobutyric acid (GABAA) ion channel.
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