Abstracts

Rationale: Lennox-Gastaut Syndrome (LGS) patients (pts) differ in disease severity in relation to seizure frequency. It is important to have efficacious treatment options including antiepileptic drugs (AEDs) even for pts with substantial seizure frequencies. We conducted a post-hoc analysis of the open-label extension trial¹ of Phase II and III studies to evaluate the long-term efficacy of clobazam (CLB) for LGS pts in relation to baseline seizure frequency.Methods: In an open-label extension (OLE) study (OV-1004),¹ LGS pts who had completed 1 of 2 RCTs OV-1002 (Phase II²) or OV-1012 (Phase III/the CONTAIN trial³) received open-label CLB. Most pts initially received 0.5 mg/kg/day (up to 40 mg/day). Dosages were then adjusted based on clinical response (efficacy and tolerability), up to 2.0 mg/kg/day (80 mg/day). Visits were at Day 1, Week 1, Months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter (through Year 6). During the week preceding each visit, parents/caregivers maintained seizure diaries. Pts outside the United States did not continue in the study beyond 24 months, per protocol, resulting in much lower pt numbers for Year 3 and beyond. Pts were grouped by quartile based on their average baseline weekly drop-seizure frequencies.Results: 267 of 306 pts from OV-1002 (61 of 68) or OV-1012 (206 of 238) entered the OLE. As of March 23, 2012, 188 (70.4%) had completed the study. 251 pts had received CLB for 6 months, 229 for 1 year, 210 for 2 years, 121 for 3 years, 54 for 4 years, 44 for 5 years, and 11 for 6 years. At entry, pts mean age was 11.3 years, and their mean time since diagnosis was 6.4 years. As previously reported, median percentage decreases (vs. baseline, or last assessment before first dose of clobazam) in average weekly drop and total seizures indicated sustained efficacy over the long term.⁴ Each quartile had ~66 pts. Ranges (drop seizures/week) were: <10 (Quartile 1), 10 31 (Quartile 2), 32 110 (Quartile 3), and 111 1,147 (Quartile 4). Median percentage decreases in average weekly seizures were similar between quartiles for both drop and total seizures (drop plus non-drop seizures). Through 5 years of therapy, >50% of pts in all 4 quartiles demonstrated 50% decreases in weekly frequency for drop seizures (table), as well as total seizures. In addition, >12% of pts in Quartile 4 (pts with most severe LGS) still achieved 100% reduction in drop seizures at the specified time points.Conclusions: Using baseline seizure counts as a surrogate for disease severity, we determined CLB was efficacious in the long term even for pts with average weekly seizure counts at baseline up to 1,147 seizures/week, and a small percentage were still able to achieve freedom from drop seizures. These results are comparable to those reported in the short term for the 15-week, Phase III CONTAIN trial.^{5 1}Ng Y-T, et al. Epilepsy Behav. 2012;25:687 94. ²Conry JA, et al. Epilepsia. 2009;50:1158 66. ³Ng YT, et al. Neurology. 2011;77:1473 81. ⁴Ng Y-T, et al. Late-Breaking Abstract #1.363, AES 2012. ⁵Isojarvi J, et al. Neurology. 2013;80(Meeting Abstracts 1):P07.176.