Effectiveness and safety of adjunctive cenobamate in people with focal‐onset epilepsy: Interim results after 24‐week observational period from the BLESS study

Abstract Objective Cenobamate is an antiseizure medication (ASM) with a dual mechanism of action that was recently approved for the treatment of focal seizures in adults. This analysis aimed to describe the outcomes at 12 and 24 weeks after starting cenobamate therapy in a real‐world setting. Methods BLESS [NCT05859854] is an ongoing, observational, retrospective and prospective cohort study to evaluate the real‐world effectiveness and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy. Subgroup analysis was performed in subjects with 2 to 3 previous ASMs (early users) and those with >3 previous ASMs (late users). Results The second interim analysis of the BLESS study included 388 participants with a median (interquartile range) age of 43.0 (31.0–54.0) years. They had a median of 6.0 (4.0–9.0) prior ASMs and a median of 7.2 (3.0–20.6) monthly seizures at baseline. The median monthly seizure frequency was reduced by 59.9% (19.2%–87.3%) from baseline to 24 weeks; 229 (59.0%) subjects had a ≥50% seizure frequency reduction, and 44 (11.3%) showed sustained seizure freedom. The proportion of participants taking ≤2 concomitant ASMs increased from 217 (56.5%) at baseline to 239 (65.7%) at 24 weeks. Among the early users ( n = 76, 19.6%), the median reduction in monthly seizure frequency at 24 weeks was 78.0% (50.0–97.1%), and 76.3% of subjects had a ≥50% response rate. The frequency of adverse drug reactions (ADRs) was 5.3% and 23.4% in early and late users. The most frequent ADRs were somnolence, dizziness, and balance disorder; after the occurrence of ADRs, 63.5% of participants maintained the prescribed dose, and 5.2% permanently discontinued treatment. Significance Cenobamate was effective in reducing seizure frequency in a real‐world setting and showed a manageable safety profile. The treatment with cenobamate also reduced the burden of concomitant ASMs in both early and late users.