By Thomas R. Collins
NEW ORLEANS—New data on the novel epilepsy drug cenobamate suggest that earlier concerns about drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome may be allayed with a slower introduction of the drug, according to a presentation here at the American Epilepsy Society annual meeting.
In the phase 3, multicenter, open-label study, 1,110 patients with uncontrolled focal seizures received cenobamate for at least six months. They were started at just 12.5 mg a day for the first two weeks, increased to 25 mg a day in weeks three and four, with doses increasing bi-weekly to 25 mg then 50 mg, until patients were at 200 mg at weeks 11 and 12, up to a maximum dose of 400 mg.
Cases of DRESS, a delayed reaction also seen with other drugs including antibiotics, were reported during the earlier stages of drug development, and this study was meant to address those concerns, said Marc Kamin, MD, chief medical officer of the New Jersey-based SK Life Science, Inc., which manufactured and funded the study. So far, no cases of DRESS have been seen, researchers reported.
"This is extremely encouraging," he said. "I think that we've learned the correct way is for physicians to use this drug so (patients) can benefit from the efficacy…. Now we know how to use the drug in the best way possible."
Otherwise, no other safety concerns have emerged, with somnolence and dizziness the most common treatment-related adverse events, researchers said. More than 80 percent of patients took cenobamate for more than six months, the team said.
Researchers also reported that time to efficacy of cenobamate is clinically evident within two to four weeks. Median seizure reduction for cenobamate has previously been reported as 35 percent to 55 percent, depending on the dosing.
The drug appears to work by inhibiting the persistent component of the sodium current and, according to a separate presentation here, through effects on the gamma-amino butyric acid receptor.
"We don't know for sure how these drugs work many times for epilepsy, but it's possible that we have two mechanisms," Dr. Kamin said.
The drug maker applied for approval with the US Food and Drug Administration at the end of November.
Robert S. Fisher, MD, PhD, FAAN, the Maslah Saul MD professor and director of the Epilepsy Center at Stanford University, said the latest safety findings are encouraging for cenobamate.
"It's always treacherous in the early run on the drug — you never know what's going to happen," he said. "So far, from someone who's quite objective about the whole thing and an outsider to this, what I've seen looks very interesting."
He said he has been particularly impressed by cenobamate's rate of seizure-freedom during the maintenance phase. Despite a large number of antiepileptic drugs, the need for more is still great, he said.
"We now have 27 antiepileptic drugs available for use in the United States, and while some people might say, enough is enough with 27 drugs, those drugs still only lead to satisfactory seizure control in two out of three people with epilepsy," he said.
Dr. Fisher had no disclosures relevant to the study.
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AES Abstract 1.303: Sperling M, Klein P, Kamin M. Safety of cenobamate (YKP3089) as adjunctive treatment for uncontrolled partial seizures in a large, multicenter, open-label study.