December 13, 2018

During development trials, 3 of 953 patients developed confirmed causes of drug reaction with eosinophilia and systemic symptoms.

NEW ORLEANS — Early results from an ongoing, multicenter, open-label safety study of cenobamate has found no cases of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in 1110 patients with epilepsy exposed to cenobamate for at least 6 months, according to research presented at the 72nd American Epilepsy Society Annual Meeting, held November 30 to December 4, 2018.

Patients aged 18 to 70 with uncontrolled focal (partial) seizures taking stable doses of 1 to 3 antiepileptic drugs were enrolled. Testing a hypothesis that a lower starting dose and slower titration rate of cenobamate than those utilized in earlier studies would mitigate the risk for serious cutaneous reactions like DRESS, investigators administered gradually increasing daily doses of cenobamate 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg/day at 2-week intervals. Biweekly increments of 50 mg/day to increase dosage to 400 mg/day were allowed.

For the first 16 weeks of the study period, patients visited every 2 weeks and then every 1 to 3 months thereafter. Patients were screened for DRESS monthly with an in-depth review of all hypersensitivity reactions.

Serious adverse events, reported in accordance with local regulatory requirements, were seen in 114 patients (8.5%), and were most commonly seizures that required hospitalization. Other common adverse events included somnolence, dizziness, and fatigue. No cases of DRESS were identified.

A total of 1347 patients had been enrolled at the time of study data cut-off; 269 patients discontinued therapy. Four deaths were reported: sudden death with no autopsy, traumatic intracerebral hemorrhage after a fall, fatal injuries after being struck by a car, and respiratory failure in a participant with Angelman syndrome. 

In addition, no cases of DRESS were reported among the patients exposed to cenobamate for at least 6 months (n=1110) and among all patients exposed to cenobamate. The most common serious adverse event was seizure, as seen in 14 patients (1.0%). The most common treatment-emergent adverse event was reported to be somnolence (28.1%), dizziness (23.65), and fatigue (16.6%); most were mild or moderate in severity. 

These early results suggest that reducing the starting dose and slowing the titration rate of cenobamate may mitigate the risk for DRESS in patients with epilepsy experiencing uncontrolled focal (partial) seizures.

This study was supported by SK Life Science, Inc. Please refer to reference for a complete list of authors’ disclosures.

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Reference

Sperling M, Klein P, Kamin M. Safety of cenobamate (YKP3089) as adjunctive treatment for uncontrolled partial seizures in a large, multicenter, open-label study. Presentation at: 72nd Annual Meeting of the American Epilepsy Society; November 30-December 4, 2018; New Orleans, LA. Poster 1.303.