WASHINGTON -- The FDA approved cenobamate (Xcopri) tablets on Thursday to treat partial-onset (focal) seizures in adults.

Cenobamate 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 of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, in a statement.

More than 30% of epilepsy patients have uncontrolled seizures. Cenobamate is believed to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents and as a positive allosteric modulator of the GABA-A ion channel, according to drug developer SK Life Science.

The FDA decision was based on two phase II trials, including one of cenobamate as adjunctive therapy reported here (results of the other phase II trial are pending publication). In these studies, 655 adult patients had partial-onset seizures with or without secondary generalization for an average of approximately 24 years, and a median seizure frequency of 8.5 seizures per 28 days during an 8-week baseline period. Compared with placebo, doses of 100, 200, and 400 mg daily of cenobamate reduced the percent of seizures over 28 days in the trials. The recommended maintenance dose of cenobamate after titration is 200 mg daily, but some patients may need an additional titration to 400 mg daily, the maximum recommended dose, the FDA said.

Several cases of a serious adverse effect known as DRESS (drug reaction with eosinophilia and systemic symptoms) were reported in cenobamate trials, and one patient died when cenobamate was titrated rapidly. That risk appears to have been mitigated, Marc Kamin, MD, chief medical officer of SK Life Science, told MedPage Today. In a phase III safety study, "no cases of DRESS syndrome were identified in 1,339 patients exposed to cenobamate using a lower starting dose of 12.5 mg and slower titration of every 2 weeks," he said. However, this finding does not show that the risk of DRESS is prevented by a slower titration, the FDA noted.

A higher percentage of patients who took cenobamate also had a shortening of the QT interval of greater than 20 milliseconds compared with placebo; cenobamate should not be used in patients with hypersensitivity to cenobamate or any of its inactive ingredients or Familial Short QT syndrome, the agency added. The most common side effects reported in clinical trials were somnolence, dizziness, fatigue, diplopia, and headaches. Patients should also be advised not to drive or operate machinery until the effect of cenobamate is known, the FDA cautioned.

In addition, antiepileptic drugs, including cenobamate, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication, the agency warned. Patients taking an antiepileptic should be monitored for depression, suicidal thoughts or behavior, and any unusual changes in mood or behavior.

New Jersey-based SK Life Science, a subsidiary of SK Biopharmaceuticals in Korea, is commercializing cenobamate in the U.S., while the Swiss company Arvelle Therapeutics holds European rights. The drug is expected to be available in the U.S. in the second quarter of 2020 following scheduling review by the Drug Enforcement Administration, in 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg once-daily doses. Cenobamate is the first compound independently discovered and developed by a Korean pharmaceutical company from inception through to FDA approval, SK said.