SK Life Science’s sodium channel antagonist cenobamate was approved based on data from pivotal trials in nearly 2000 patients in which it reduced the median number of seizures per 28 days.
Michael Sperling, MD
The FDA has granted approval to cenobamate
(Xcopri, SK Life Science) for the treatment of partial-onset seizures in adults. The approval was supported by data from pivotal trials that assessed the efficacy and safety of cenobamate in more than 1900 patients.1
It was shown in trials to significantly reduce partial-onset seizure frequency, with up to 20% of patients achieving seizure-free status during the maintenance phases. The therapy is expected to be available in the US in the second quarter of 2020, following scheduling review by the DEA, according to SK Life Science.2
“Xcopri is a new option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life,” said Billy Dunn, MD, director, Office of Neuroscience, FDA Center for Drug Evaluation and Research, in a statement. “Patients can have different responses to the various seizure medicines that are available. This approval provides an additional needed treatment option for people with this condition.”
The safety and efficacy of the sodium channel antagonist were established in 2 pivotal trials (Study 013 and Study 017) 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 per 28 days.
“The approval of Xcopri will provide clinicians with an effective medication for our patients who are continuing to have focal (partial-onset) seizures,” Michael Sperling, MD, director, Jefferson Comprehensive Epilepsy Center, and Jefferson Clinical Neurophysiology Laboratory, and an investigator in the therapy’s clinical trial program, said in a statement. “It is very encouraging to see that patients receiving Xcopri saw significant reductions in the frequency of seizures, with some even achieving zero seizures.”
The FDA stated in its release that the recommended maintenance dose of Xcopri post-titration is 200 mg daily. Some patients may require titration to 400 mg daily, which is the maximum recommended dose, based on their clinical response and tolerability.
In 1 of the 2 pivotal trials, presented at the 2018 American Academy of Neurology Annual Meeting—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.
Marc Kamin, MD, the chief medical officer at SK Life Science, told NeurologyLive at the time of the NDA submission
in February that SK Life Science is “hopeful it will provide an additional option for these patients.”
“We know significant unmet needs remain for patients with CNS disorders, particularly epilepsy,” he said. “Currently, about one-third of the epilepsy patient population does not achieve adequate seizure control with currently available treatments.”
Additionally, due to 3 incidences of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in early phase study, the therapy was assessed to determine the ability to mitigate this risk. In a trial 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
Sperling told NeurologyLive in an interview
that cenobamate is one of the more impressive therapies he's worked with. “This drug, based on my opinion after treating more than 60 patients, is the most startlingly effective anticonvulsant drug that I've ever used in an investigational trial. I've been involved in investigational trials since the late 1980s and this one remarkably reduces seizure frequency and seizure severity. I have seen a number of patients who have become seizure-free after starting this drug," he said.
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.
3. 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. sklifescienceinc.com/pdf/SKLSI%20NDA%20Acceptance%20Press%20Release%20-FINAL-Updated%202-3-19.pdf. Accessed November 21, 2019.
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.