Cenobamate Associated with Higher Response Rates than Other ASMs in Drug-Resistant Focal Epilepsy
KEY TAKEAWAYS
- Cenobamate was associated with higher adjusted responder rates than brivaracetam, lacosamide, and perampanel.
- Seizure freedom at 12 months also favored cenobamate, though adverse effects were reported more often.
Treatment with Xcopri (cenobamate; SK Life Science, Paramus, NJ) was associated with higher adjusted responder rates and seizure freedom compared with brivaracetam, lacosamide, and perampanel in adults with drug-resistant focal epilepsy, according to results from a multicenter real-world analysis published in JAMA Neurology. The findings suggest that cenobamate may offer greater long-term effectiveness than several other newer-generation antiseizure medications (ASMs), although adverse effects were more common and should be considered in treatment decisions.
The pooled retrospective analysis included 1993 ASM prescriptions from 1949 participants treated at 71 epilepsy centers between January 2017 and January 2024. Eligible participants were aged 16 years or older and had drug-resistant focal epilepsy, defined as failure to achieve sustained seizure freedom despite adequate trials of at least 2 appropriately chosen and dosed ASMs. Treatments evaluated as adjunctive therapy included Xcopri, brivaracetam, lacosamide, and perampanel. The primary end point was ≥50% seizure reduction at 6 months; secondary end points included 12-month responder rate, seizure freedom, 12-month retention, and adverse effects.
Key Findings
- Adjusted predicted probability of ≥50% response at 6 months was highest with Xcopri (0.82; 95% CI, 0.73 to 0.88), compared with lacosamide (0.57), perampanel (0.54), and brivaracetam (0.45).
- At 12 months, adjusted predicted probability of ≥50% response was 0.84 with Xcopri, 0.56 with perampanel, 0.52 with lacosamide, and 0.45 with brivaracetam.
- Adjusted predicted probability of ≥6-month seizure freedom at 12 months was 0.32 with Xcopri vs 0.17 with lacosamide, 0.16 with perampanel, and 0.11 with brivaracetam.
- Xcopri had the highest rate of adverse effects during follow-up (57.8%), whereas lacosamide had the lowest (14.8%).
- Xcopri treatment was associated with higher adjusted retention than brivaracetam and perampanel at 12 months, with no significant difference vs lacosamide.
Source
Cerulli Irelli E, Roberti R, Borioni MS, et al. Comparative effectiveness of brivaracetam, cenobamate, lacosamide, and perampanel in focal epilepsy. JAMA Neurol. 2026;83(4):320-328. doi:10.1001/jamaneurol.2025.5625.