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The chief medical officer at SK Life Science discussed what the sodium channel antagonist will offer those treating partial-onset seizures.
Marc Kamin, MD
With the recent FDA decision to approve cenobamate (Xcopri, SK Life Science) for partial-onset seizures in adults, these patients—who are often refractory to available medications—will gain benefit from yet another option.
The therapy is expected to be available in the US in the second quarter of 2020, following scheduling review by the DEA. FDA approval was supported by data from pivotal trials that assessed the efficacy and safety of cenobamate in more than 1900 patients, in which it was shown to significantly reduce partial-onset seizure frequency, with up to 20% of patients achieving seizure-free status during the maintenance phases.1,2
To find out more about what the sodium channel antagonist will offer those treating epilepsies, NeurologyLive spoke with Marc Kamin, MD, chief medical officer, SK Life Science.
Marc Kamin, MD: We’re very pleased that the FDA has approved Xcopri and believe it will be an important new treatment option for adults with partial-onset seizures. Nearly 40% of people with partial-onset seizures continue to have seizures, despite the use of available anti-epileptic drugs. The patients in our trials had uncontrolled seizures and we saw that when Xcopri was added to their usual therapy regimen of 1 to 3 antiepileptic drugs, they experienced statistically significant reductions in median seizure frequency, compared to when placebo was added. Additionally, an encouraging number of patients in our trials achieved 0 seizures during the maintenance phase.
While the precise mechanism by which Xcopri exerts its therapeutic effect is unknown, it is believed to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. It is also a positive allosteric modulator of the γ-aminobutyric acid (GABAA) ion channel.
The data points that are most encouraging to me and many of the clinical trial investigators we have worked with are the rates of 0 seizures we saw in the maintenance phase of Study 013 and Study 017. In the maintenance phase of Study 017, we saw that 11% of those in the 200 mg/day group, and 21% of those in the 400 mg/day group achieved zero seizures, compared to 1% for patients on placebo.
Our large, phase 3 multi-center, open-label safety study of adults with partial-onset seizures found that reducing the starting dose (to 12.5 mg) and slowing the titration rate of Xcopri to 2-week intervals appeared to mitigate the risk of DRESS in trial participants. In the study, there were no cases of DRESS observed in 1339 patients treated with Xcopri, including 1110 treated with Xcopri for more than 6 months.
Patients and their healthcare providers should follow the dosing recommendations in the label, which note that Xcopri should be initiated at 12.5-mg once daily and titrated every 2 weeks.
Xcopri is currently being investigated in adult patients with primary generalized tonic-clonic seizures in a phase 3 clinical trial. Additionally, beyond Xcopri, we have other compounds in our pipeline that are in development for the treatment of central nervous system disorders, including epilepsy and Lennox-Gastaut syndrome, which have all been discovered in-house. We will continue to look at areas of significant unmet need to determine how our capabilities in R&D for central nervous system disorders can have the most impact.
Transcript edited for clarity.
1. FDA approves new treatment for adults with partial-onset seizures [press release]. Silver Spring, MD: FDA; Published November 21, 2019. fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-partial-onset-seizures. Accessed November 21, 2019.
2. FDA Approves Xcopri® (cenobamate tablets), an Anti-Epileptic Drug (AED) from SK Biopharmaceuticals, Co., Ltd., and U.S. Subsidiary SK Life Science, Inc. [press release]. Paramus, NJ: SK Life Science; Published November 21, 2019. multivu.com/players/English/8611851-sk-life-science-fda-approval. Accessed November 21, 2019.