SK Life Science has announced that its newly approved treatment for partial-onset seizures in adults, cenobamate (Xcopri) has been designated as a Schedule V medicine by the DEA, the lowest designation for abuse from the agency.1
The sodium channel antagonist was originally approved by the FDA for this indication in late November 2019, with the approval supported by data from pivotal trials that assessed the efficacy and safety of cenobamate in more than 1900 total patients.2 It was shown to significantly reduce partial-onset seizure frequency, with up to 20% of patients achieving seizure-free status during the maintenance phases.
"With the DEA's decision to designate XCOPRI as a Schedule V medicine, the final step of the regulatory approval process is complete," Jeong Woo Cho, PhD, President and CEO of SK Biopharmaceuticals and SK Life Science, said in a statement. "We are moving forward to launch Xcopri as planned in the second quarter of 2020 and remain steadfast in our commitment to addressing unmet needs for patients with epilepsy."
The safety and efficacy of cenobamate were established in 2 pivotal trials including 655 adults with partial-onset seizures with or without secondary generalization. Patients experienced these seizures for a mean of 24 years, with a median of 8.5 seizures per 28 days during the baseline period of 8 weeks. Patients were randomized to doses of 100, 200, and 400 mg compared to placebo, with the therapy reducing the median number of seizures.3
In 1 of the 2 pivotal trials, an 18-week, randomized double-blind, dose-response study, 437 patients received 100 mg cenobamate (n = 108), 200 mg (n = 110), 400 mg (n = 111), or placebo (n = 108). Median seizure frequencies decreased for all doses of cenobamate, with the 100 mg/day experiencing a 35.5% reduction, the 200 mg/day observing a 55.0% reduction, and the 400 mg/day seeing a 55.0% reduction. In comparison, the placebo group experienced a 24.0% reduction.3
The median frequencies for simple partial seizures also decreased with all doses of cenobamate (100 mg: 48.0%; 200 mg: 63.0%; and 400 mg: 58.5%) compared with placebo, which showed a 7.0% reduction. The median frequencies for complex partial seizures and secondary generalized tonic-clonic seizures decreased with the 200-mg dose, 55.0% and 91.0%, respectively, as well as the 400-mg dose, 60.0% and 78.0%, respectively. In comparison, the placebo group observed 28.5% and 33.0% reductions, respectively.
Due to 3 cases of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in early-phase study of cenobamate, a study was undertaken to determine the ability to mitigate this risk. Including more than 1300 patients, gradually increasing doses of cenobamate—12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg—were administered daily at 2-week intervals. Biweekly increases of 50 mg/day to increase the dosage to 400 mg/day were allowed. No incidences of DRESS were observed in the phase 3 trial.4
1. SK life science Receives Schedule V Designation from DEA for XCOPRI® (cenobamate tablets) [press release]. Paramus, NJ: Published March 10, 2020. Accessed March 10, 2020. prnewswire.com/news-releases/sk-life-science-receives-schedule-v-designation-from-dea-for-xcopri-cenobamate-tablets-301020783.html
2. FDA approves new treatment for adults with partial-onset seizures [press release]. Silver Spring, MD: FDA; Published November 21, 2019. Accessed March 10, 2020. fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-partial-onset-seizures.
SK life science announces FDA acceptance of NDA submission for cenobamate, an investigational antiepileptic drug [press release]. Fair Lawn, NJ: SK Life Science; Published February 4, 2019. Accessed March 10, 2020. sklifescienceinc.com/pdf/SKLSI%20NDA%20Acceptance%20Press%20Release%20-FINAL-Updated%202-3-19.pdf.
4. Sperling M, Klein P, Kamin M. Safety of cenobamate (YKP3089) as an adjunctive treatment for uncontrolled partial seizures in a large, multi-center, open-label study. Presented at: American Epilepsy Society Annual Meeting; New Orleans, LA; December 2, 2018. aesnet.org/meetings_events/annual_meeting_abstracts/view/500991.