Cenobamate Demonstrates Sustained Efficacy in Asian and Chinese Patients with Focal Seizures
核心洞察
Open-label extension data from a 52-week study confirms cenobamate maintains or improves seizure reduction across all focal seizure subtypes in Asian patients, with responder rates ranging from 70% to 78%.
Chinese subgroup analysis reveals dose-dependent efficacy with median seizure frequency reductions of 39.5%, 88.0%, and 100% for 100mg, 200mg, and 400mg doses respectively, compared to 24.6% with placebo.
Cenobamate demonstrated consistent efficacy regardless of concomitant antiseizure medication mechanisms or number, with seizure freedom achieved in up to 59.6% of patients at the highest dose.
Cenobamate continues to demonstrate robust efficacy in Asian patients with uncontrolled focal seizures (搜索), according to new data from an ongoing 52-week open-label extension study and a comprehensive Chinese subgroup analysis presented at the 2025 American Epilepsy Society (搜索) Annual Meeting.
Sustained Benefits in Open-Label Extension
The open-label extension (OLE) of the multinational phase 3 study YKP3089C035 enrolled 231 Asian adults with focal seizures (搜索) who had experienced at least 8 seizures during an 8-week baseline period despite treatment with 1 to 3 antiseizure medicines. After an 18-week blinded conversion to a target cenobamate dose of 400 mg/day, 184 patients entered the 32-week maintenance phase.
Results from the OLE maintenance phase showed substantial reductions in median seizure frequency per 28 days across all assessed seizure subtypes. Responder rates during the maintenance phase demonstrated that the majority of patients experienced at least a 50% reduction in seizure frequency, with overall responder rates ranging from approximately 70% to 78% depending on the subtype.
Seizure freedom rates were particularly notable for focal to bilateral tonic-clonic (FBTC) seizures at 55.6% (25/45), compared to 29.1% (46/158) for focal impaired awareness (FIA) seizures and 19.2% (5/26) for focal aware motor (FAM) seizures.
Chinese Population Shows Strong Response
A detailed subgroup analysis of 227 Chinese participants from the same phase 3 study revealed dose-dependent improvements in seizure control. The median percentage reduction in focal seizure frequency during the maintenance phase was 39.5%, 88.0%, and 100% for the 100mg, 200mg, and 400mg dose groups respectively, compared to 24.6% with placebo (p = 0.012, p < 0.001 and p < 0.001 vs. placebo, respectively).
Responder rates improved dramatically with higher cenobamate doses. During the maintenance phase, ≥50% responder rates were achieved by 35.4% in the 100mg group, 76.0% in the 200mg group, and 89.4% in the 400mg group, compared to only 22.0% with placebo. Seizure freedom was achieved by 10.4%, 40.0%, and 59.6% of patients in the 100mg, 200mg, and 400mg groups respectively, versus 4.0% with placebo.
Efficacy Across Different Treatment Combinations
The analysis revealed that cenobamate maintained efficacy regardless of concomitant antiseizure medication mechanisms. Among participants receiving sodium channel blockers (SCBs), which comprised 91.1% of the study population, median seizure frequency reductions were 37.5%, 80.0%, and 100% for the 100mg, 200mg, and 400mg doses respectively, compared to 23.3% with placebo.
For the smaller non-SCB group (8.9% of participants), median reductions were 81.1% with 100mg cenobamate and 100% with both 200mg and 400mg doses, compared to 56.5% with placebo.
The drug also demonstrated consistent efficacy across different numbers of concomitant medications. Among patients receiving one concomitant ASM, seizure frequency reductions were 71.5%, 94.2%, and 100% for the three cenobamate doses, while the placebo group experienced a 49.3% increase in seizure frequency.
Dual Mechanism of Action Drives Efficacy
Cenobamate's superior efficacy profile stems from its dual mechanism of action. The drug acts as a preferential inhibitor of persistent sodium currents in voltage-gated sodium channels (搜索), reducing repeated neuronal firing associated with seizures. Additionally, it functions as a positive allosteric modulator of GABAA receptors (搜索), enhancing inhibitory signaling in the brain.
This mechanism distinguishes cenobamate from other antiseizure medications such as lamotrigine, felbamate, and carbamazepine, which primarily target transient sodium currents. While phenytoin, topiramate, and valproate block both transient and persistent sodium currents, they have much weaker effects on persistent currents compared to cenobamate.
Safety Profile Remains Favorable
The safety profile in both studies was consistent with previous cenobamate trials. In the Chinese subgroup analysis, the most common treatment-emergent adverse events were dizziness (ranging from 27.3% to 63.2% across dose groups), somnolence (10.9% to 35.1%), and elevated gamma-glutamyl transferase levels (20.0% to 33.3%).
Serious treatment-emergent adverse events were rare, reported in 1.8% each in the 100mg and 200mg groups and 7.0% in the 400mg group. No cases of drug reaction with eosinophilia and systemic symptoms (DRESS) or adverse events leading to death were reported.
Clinical Implications for Asian Populations
These findings are particularly significant for Asian epilepsy (搜索) management, where treatment patterns differ from Western populations. In China, classic drugs such as valproate, carbamazepine, and oxcarbazepine are typically used as first-line treatments, while newer antiseizure medications like levetiracetam and lamotrigine are often reserved for second-line therapy.
The study showed that cenobamate was effective when combined with the most commonly used drugs in the Chinese population, including oxcarbazepine (36.9%), levetiracetam (38.2%), and sodium valproate (36.0%). This compatibility with existing treatment patterns could facilitate adoption in clinical practice.
Dr. William E. Rosenfeld, Director at The Comprehensive Epilepsy Care Center (搜索) for Children and Adults in St. Louis, Missouri, who led the open-label extension study, noted that the findings validate cenobamate's broad effectiveness profile across different patient populations and seizure subtypes.
The cumulative retention rates in the extension study were 71%, 60%, and 56% at 1 year, 2 years, and 3 years respectively, indicating sustained tolerability over extended treatment periods. At the final visit, 28.7%, 18.8%, and 11.8% of patients had remained seizure-free for at least 1 year, 2 years, and 3 years respectively.
These comprehensive data sets provide strong evidence for cenobamate's efficacy and safety in Asian populations with focal seizures (搜索), potentially addressing significant treatment gaps in epilepsy (搜索) management across the region. With approximately nine million people affected by epilepsy in China alone and treatment gaps ranging from 62.6% to 97.0% across different regions, effective new treatment options are critically needed.