Cenobamate Offers Unique Benefit for Surgically Refractory Epilepsy

William Rosenfeld, MD

A post hoc analysis presented at the 2021 American Epilepsy Society (AES) Annual Meeting, December 3-7, in Chicago, Illinois, showed that treatment with cenobamate (Xcopri; SK Life Science) provides additional seizure freedom (SF) benefit for patients with uncontrolled focal seizures taking 1-3 antiseizure medications (ASMs) who were refractory to a prior epilepsy-related surgery.

The data was from the long-term, phase 3, open-label C021 safety study (NCT02535091), which included 1347 patients aged 18-70 years old. In this analysis, senior author William Rosenfeld, MD, neurologist, Comprehensive Epilepsy Care Center for Children and Adults, in St. Louis, Missouri, and colleagues recorded the percentage of patients achieving seizure freedom for at least 12 months until last clinic visit and those who achieved SF after 12 months at any interval, not just at last visit.

The trial began in July 2016 and had a total study duration of up to 43 months, with data cutoff on September 1, 2019. In total, 240 patients had focal seizure data available, of which 177 were still receiving study drug as of data cut-off. Mean duration of time on-study for those patients was 33.6 months. Eighty-five (35.4%) of the available cohort had prior epilepsy-related surgery, and in this group, 23.5% (20 of 85) achieved seizure freedom for at least 12 months since last clinic visit while 30.6% had seizure freedom for at least 12 months during any interval.

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Rosenfeld noted that these results should give clinicians the confidence to prescribe cenobamate more for this patient population. "We’ve come very far with our seizure surgery, and it’s become safer and safer, but there’s still risks whenever you perform a surgery. If you can give a medicine and control the patient in that way, that’s fantastic, and avoids the potential risks of surgery," he told NeurologyLive®.

The cohort included 31 patients who had been treated with only vagus nerve stimulation (VNS)/responsive neurostimulation (RNS); 40 patients who had at least 1 procedure that was not VNS/RNS; and 14 patients who had both VNS and a resection, ablation, or disconnection surgery. Across all surgical procedures, the percentage of those on cenobamate with seizure freedom for at least 12 months ranged between 20% to 35.7%.

"From a surgical aspect, it works on these folks. I’d go out on a limb and say that within the distant future, it will be almost mandatory that you try cenobamate as one of those drugs before seizure surgery," Rosenfeld added. “Obviously, that will be up for opinion and debate, but I think that with the efficacy numbers we’ve seen between that 20% to 35% seizure rate, that’s quite good news."

Of the 177 patients still receiving cenobamate, 65 had prior epilepsy-related surgery, with a mean duration of 23.5 months at data cutoff. At this time point, 29.2% (19 of 65) had SF for at least 12 months. For nonsurgical patients (n = 155), 26.5% (n = 41), 27.1% (n = 42) and 39.4% (n = 61) of patients achieved SF for at least 12 months at data cutoff, last clinic visit, and at any consecutive interval, respectively.

Since it became FDA-approved in 2019 to treat partial-onset seizures, there has been an abundance of data to further bolster cenobamate’s safety and efficacy profile, including 2 post hoc analyses from C021 published in October. These data showed that long-term treatment with cenobamate lasting up to 40.2 months was provided safe and effective reduction of seizure frequency and was associated with concomitant antiseizure medication dose reductions.²

SK Life Science presented a total of 6 abstracts at AES 2021, including data on the effects of cenobamate by focal seizure subtypes, those with uncontrolled focal seizures in routine clinical practice, and durability of seizure control with adjunctive cenobamate. They also presented a meta-analysis/indirect comparison of cenobamate to other antiseizure medications for the treatment of uncontrolled focal seizures as well as data on patients’ plasma concentrations after reaching at least 50% or 100% responder rates over a year period.³

For more coverage of AES 2021, click here.

REFERENCES

1. Abou-Khalil B, Aboumatar S, Klein P, Krauss GL, Sperling MR, Rosenfeld WE. Efficacy of cenobamate for uncontrolled focal seizures in patients with previous epilepsy-related surgery: post hoc analysis of a phase 3, multicenter, open-label study. Presented at 2021 AES Annual Meeting; December 3-7; in Chicago, IL. Abstract 2.206

2. Epilepsia publishes 2 post-hoc analyses from long-term study of Xcopri (cenobamate tablets) CV. News release. SK Life Science. October 12, 2021. Accessed December 8, 2021. https://www.sklifescienceinc.com/pdf/Epilepsia_Publishes_Two_Post-hoc_Analyses_From_Long-Term_Study_Of_XCOPRI%C2%AE_%28cenobamate%20tablets%29_CV%20%281%29.pdf

3. SK Life Science to present latest Xcopri (cenobamate tablets) CV data at the American Epilepsy Society 2021 Annual Meeting. News release. SK Life Science. November 29, 2021. Accessed December 8, 2021. https://www.sklifescienceinc.com/pdf/SK%20life%20science%20To%20Present%20Latest%20XCOPRI%C2%AE%20%28cenobamate%20tablets%29%20CV%20Data%20at%20the%20American%20Epilepsy%20Society%202021%20Annual%20Meeting.pdf