Cenobamate Demonstrates High Rates of Long-Term Retention in Refractory Epilepsy

Jacqueline A. French, MD

Newly published data from an open-label extension (OLE) of the 12-week C013 study (NCT01397968) showed significant long-term retention of adjunctive cenobamate (Xcopri; SK Life Science) for up to 7.8 years in adults with treatment-resistant focal seizures taking 1 to 3 antiseizure medications (ASMs).^1,2

The OLE of the original multi-center, double-blind, placebo controlled study included 149 adults with uncontrolled focal seizures who had median treatment duration of 6.25 years with cenobamate. As of the data cut-off in July 2019, 57% (n = 85) of patients remained in the OLE (median treatment duration, 6.8 years [range, 6.4-7.8]). The median modal daily cenobamate dose was 200 mg (range, 50-400).

Based on a Kaplan-Meier analysis, the probability of continuing treatment was 73% after 1 year, 67% after 2 years, 63% after 3 years, 61% after 4 years, 60% after 5 years, and 59% after 6 years. Among the patients who continued treatment at 1 year (n = 107), the probability of continuing treatment was 92% after 2 years, 87% after 3 years, 83% after 4 years, and 82% after 5 years.

"In this long-term evaluation with cenobamate, we observed high retention rates beyond 6 years in a real-life clinical setting in which patients received individualized doses of both cenobamate and other anti-seizure medications,” Jacqueline A. French, MD, professor of neurology, NYU Langone Comprehensive Epilepsy Center, director, Epilepsy Study Consortium, and chief medical and innovation officer, Epilepsy Foundation, said in a statement.1 “Because refractor epilepsy is a chronic, difficult to manage condition requiring ongoing treatment, the long-term retention rates represent an important and encouraging clinical outcome reflecting the safety, tolerability, and effectiveness of cenobamate.”

READ MORE: New tES System Gets Breakthrough Designation in Refractory Focal Epilepsy

In patients who continued cenobamate at 12 months, 79.4% (n = 85) were still receiving the therapy after a median duration of 6.8 years. The most common reasons for discontinuation, which occurred in 40.9% of the total patient population (n = 61), were withdrawal by patient (19.5%; n = 29), adverse event (AE; 10.1%; n = 15), lack of efficacy (5.4%; n = 8). No specific reasons were recorded for the “withdrawal by patient” category.

In the OLE, 53.7% (n = 80) of patients discontinued and remained off 1 or more concomitant ASMs while 26.2% (n = 39) of patients added 1 or more concomitant ASMs. Among the 80 patients who discontinued and remained off 1 or more concomitant ASMs, 76.3% (n = 61) remained in the OLE at the data cutoff.

Treatment-emergent AEs (TEAEs) occurred in 89.3% (n = 133) of patients throughout the 7.8-year duration of the OLE, most of which were mild (28.2%) or moderate (47%) in severity. Dizziness (32.9%; n = 49), headache (26.8%; n = 40), and somnolence (21.5%; n = 32) were the most frequently reported TEAEs. Additionally, the timing for the onset of the most common TEAEs showed the median onset for dizziness was 36 days, for somnolence was 41 days, and for fatigue was 57.5 days, compared to the median onset of headache which was 354 days.

A total of 25.5% (n = 38) of patients experienced serious TEAEs, 10.1% (n = 15) of which led to discontinuation of treatment. Seizure (n = 6), vomiting, pneumonia, sepsis, and osteoarthritis (n = 2 each), were among serious TEAEs that occurred in more than 1% of patients. There were 3 deaths in the study, including 1 patient who passed from sudden death in epilepsy rated as unlikely to be related to study treatment, 1 cardiac arrest resulting in death rated as not related to study treatment, and 1 completed suicide rated as unlikely to be related to study treatment.

Cenobamate was granted FDA approval for the treatment of partial-onset seizures in November 2019. The therapy can be combined with other ASMs or used alone. Shortly after the approval, French sat down with NeurologyLive to provide her thoughts on the drug’s future impact on seizure control. Watch the interview below to learn more about cenobamate’s potential.

REFERENCES

1. Long-term safety and tolerability of Xcopri (cenobamate tablets) CV published in epilepsia. July 20, 2021. Accessed July 21, 2021. https://www.prnewswire.com/news-releases/long-term-safety-and-tolerability-of-xcopri-cenobamate-tablets-cv-published-in-epilepsia-301337001.html

2. French JA, Chung SS, Krauss G, et al. Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: open-label extension of a randomized clinical study. Epilepsia. Published online July 13, 2021. doi: 10.1111/epi.17007