Post hoc analyses from an open-label study showed that seizure frequency was significantly reduced and the seizure-freedom rate was significantly improved among 240 adult participants who received cenobamate. The patients’ use of concomitant antiseizure medications was also reduced, with no effect on efficacy.
These results are “fascinating” and “very, very exciting,” said lead author William E. Rosenfeld, MD, director, Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Mo. Although responder rates were impressive, at 50% or greater and 75% or greater, “what patients really want is to have seizure freedom, or at least a 90% reduction in seizures,” Dr. Rosenfeld said.
The findings were presented at the annual meeting of the American Epilepsy Society, held online this year.
Adverse events
Cenobamate reduces seizures by inhibiting sodium current or affecting the GABAA channel, or potentially through a combination of these two mechanisms, said Dr. Rosenfeld. The drug was approved by the U.S. Food and Drug Administration in November 2019 for the treatment of uncontrolled partial-onset seizures in adults, which represent about 60% of all epileptic seizures. It has been on the market since May 2020.
During the drug’s development, three cases of drug reaction with eosinophilia and systemic symptoms (DRESS) occurred. This condition typically involves a skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities, including a high level of eosinophils. However, an open-label study, published earlier this year in Epilepsia, that assessed safety and pharmacokinetics in 1,347 patients aged 18-70 years who received stable doses of one to three antiseizure medications showed that, with “slow and low titration” of cenobamate, there were no cases of DRESS, Dr. Rosenfeld said.
In that safety study, investigators administered increasing daily doses of cenobamate at 12.5, 25, 50, 100, 150, and 200 mg/day at 2-week intervals. If necessary, the dose could be increased to 400 mg/day via 50-mg/day increments every other week.
The researchers presented post hoc analyses regarding 240 patients from 10 U.S. sites who participated in the safety study. Dr. Rosenfeld noted, “These are all good epilepsy centers, and they all kept seizure records.” Of these participants, 177 continued taking the drug as they had at their last visit for a mean of more than 30 months; for some, it was up to 44 months.
“So we had a 73.8% retention rate over the course of the open label, which is the maintenance phase of the study,” Dr. Rosenfeld said.
Among the entire group of 240 patients, 25.8% had been seizure free for more than 12 months at their last visit. Of the 177 who continued to take cenobamate, 33.9% were seizure free for an average of 23.5 months.
“We have never seen those kinds of numbers in the past,” said Dr. Rosenfeld, adding, “it’s so important for patients to get seizure freedom.” These promising results may be related to the fact that the drug works on more than one mechanism of seizure, he speculated.
For some patients, the drug will “make a big difference” by providing them with the best quality of life and allow them to resume normal activities, Dr. Rosenfeld noted. In addition, the drug was well tolerated. The most common adverse events were dizziness/diplopia and sleepiness/drowsiness.
