DAY 1 | Individuals with Focal Epilepsy Achieved Long-Term Seizure Freedom with Azetukalner

A post-hoc analysis from the open-label extension of a phase 2b trial enrolling adults with focal onset seizures (FOS) showed that azetukalner, a Kv7 potassium channel opener, helped patients achieve long periods of seizure freedom and regain seizure control after breakthrough seizures.

Epilepsy often follows a fluctuating clinical course, with patients achieving, losing, and regaining seizure control during various periods over their lifetime. Understanding the patterns of seizure freedom following breakthrough seizures may help providers and patients set realistic treatment goals and manage their expectations regarding outcomes, as well as plan long-term seizure management beyond a single standardized period of seizure freedom.

Azetukalner is a potent, selective Kv7 potassium channel opener that is currently being evaluated in the ongoing 7-year X-TOLE open-label extension study enrolling adults with FOS. Danielle Becker, MD, associate professor of neurology at The Ohio State University Wexner Medical Center, and colleagues conducted a post-hoc analysis of long-term data collected from X-TOLE participants treated up to 4 years, seeking to understand how seizure-free intervals are achieved and maintained in this patient population. Of the 285 participants who completed the X-TOLE double-blind period, 275 enrolled in the open-label extension phase, and 131 participants continued treatment with azetukalner 20 mg once daily for at least 48 months. As of October 6, 2025, 122 patients still participated in the open-label study.

The analysis showed that nearly half of the 131 participants (47%) who had been treated for at least 48 months in the extension phase of the trial attained periods of at least 6 consecutive months of seizure freedom. Moreover, more than one-quarter of those participants remained seizure-free for at least 12 consecutive months at the time of their last study visits. Seizure freedom, defined as a 100% reduction in seizures from the baseline in the extension phase, was assessed at specified intervals during the study.

“We have the opportunity to look at the [long-term] data and see what percentage of the patient population [achieved] complete seizure control, or seizure freedom,” said co-author Lee Gervitz, PhD, who presented the analysis during a scientific poster session at the 2025 American Epilepsy Society Annual Meeting, in Atlanta, Georgia. “For the 27% of [the participants who] were in seizure freedom for at least 1 year, how long did it last? What we found was that 75% of these patients had seizure control for 2 years and 64% of them had full seizure control up to 3 years from the last visits.” 

The findings showed that, even when patients relapsed, many of them were able to attain new, prolonged periods of seizure freedom. "We wanted to know what happens to patients who have an initial period of seizure control for 6 months,” Gervitz said. “We know that some of these patients are going to have a subsequent seizure. Forty-seven percent of the patients who were in the study for 48 months had seizure control for at least 6 months, but then half of those had a seizure. What happens to them after they have that seizure? [The results showed that] 70% of them were able to regain a period of seizure control that was at least 6 months long, and 57% of them were able to get another period of seizure control that was greater than or equal to 12 months. The mean duration of regained [seizure control] was 19 months.” 

Gervitz noted that the data available so far suggest that azetukalner has the potential to maintain long-term seizure freedom in this hard-to-treat population. “These are the kind of things that happen in everyday clinical practice, where clinicians start somebody on a medication, they are doing well, but they may have a [subsequent] seizure,” he added. “What do you do with these patients after that? [These findings show that] they have a good probability to regain seizure control.” The high proportions of patients who were able to achieve long-term seizure control after breakthrough seizures suggest that assessing a single continuous period of seizure freedom may underestimate the full scope of treatment response over time, the authors concluded.