"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, M.D., director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research. "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."
A seizure is a usually short episode of abnormal electrical activity in the brain. Seizures can cause uncontrolled movements, abnormal thinking or behavior, and abnormal sensations. Movements can be violent, and changes in consciousness can occur. Seizures occur when clusters of nerve cells (neurons) in the brain undergo uncontrolled activation. A partial-onset seizure begins in a limited area of the brain.
The safety and efficacy of XCOPRI to treat partial-onset seizures was established in two randomized, double-blind, placebo-controlled studies that enrolled 655 adults. In these studies, patients had partial-onset seizures with or without secondary generalization for an average of approximately 24 years and median seizure frequency of 8.5 seizures per 28 days during an 8-week baseline period. During the trials, doses of 100, 200, and 400 milligrams (mg) daily of XCOPRI reduced the percent of seizures per 28 days compared with the placebo group. The recommended maintenance dose of XCOPRI, following a titration (medication adjustment) period, is 200 mg daily; however, some patients may need an additional titration to 400 mg daily, the maximum recommended dose, based on their clinical response and tolerability.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported among patients taking XCOPRI. In the clinical trials, some patients experienced DRESS, and one patient died, when XCOPRI was titrated rapidly (weekly or faster titration). No cases of DRESS were reported in an open-label safety study of 1,339 epilepsy patients when XCOPRI was started at 12.5 mg per day and adjusted every two weeks; however, this finding does not show that the risk of DRESS is prevented by a slower titration. A higher percentage of patients who took XCOPRI also had a shortening of the QT interval (an assessment of certain electrical properties of the heart) of greater than twenty milliseconds compared to placebo. XCOPRI should not be used in patients with hypersensitivity to cenobamate or any of the inactive ingredients in XCOPRI or Familial Short QT syndrome. QT shortening can be associated with ventricular fibrillation, a serious heart rhythm problem.
Antiepileptic drugs (AEDs), including XCOPRI, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients taking an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. XCOPRI may cause neurological adverse reactions, including somnolence (sleepiness) and fatigue, dizziness, trouble with walking and coordination, trouble with thinking, and visual changes. Patients should also be advised not to drive or operate machinery until the effect of XCOPRI is known.
The most common side effects that patients in the clinical trials reported were somnolence (sleepiness), dizziness, fatigue, diplopia (double vision), and headaches.
The FDA granted the approval of XCOPRI to SK Life Science, Inc.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
SOURCE U.S. Food and Drug Administration