Azetukalner (FOS)

Azetukalner for Focal Onset Seizures

Potassium channels play a major role in the control of neuronal excitability and represent a promising treatment target for epilepsy. Xenon’s Phase 3 epilepsy program includes two ongoing Phase 3 clinical trials, X-TOLE2 and X-TOLE3, in focal onset seizures, or FOS.

For those living with focal-onset seizures, you may be eligible to enroll one of our ongoing Phase 3 clinical trials. Learn more here.

Phase 3 X-TOLE2 & X-TOLE3 Study Design

X‑TOLE2 and X‑TOLE3 are two identical Phase 3, multicenter, randomized, double-blind, placebo-controlled trials to evaluate the clinical efficacy, safety, and tolerability of azetukalner as adjunctive treatment in adults aged ≥18 years diagnosed with FOS who are taking 1 to 3 antiseizure medications, or ASMs.

Approximately 360 eligible subjects per trial will be randomized 1:1:1 (azetukalner 25 mg : 15 mg : placebo taken once-daily with food with no titration period).

Screening/baseline period: Up to 9.5 weeks duration to assess the frequency of seizures.

Double-blind period (DBP): 12 weeks duration. There is no titration period.

Follow-up period: 8 weeks duration after the last dose of study drug for subjects who do not complete the 12-week DBP or who complete the DBP but do not enter the open-label extension (OLE) study.

On completion of the double-blind period in X‑TOLE2 or X‑TOLE3, eligible patients may enter an OLE study for up to three years.

Primary efficacy endpoint

Median percent change in monthly focal seizure frequency from baseline to DBP of azetukalner compared to placebo.

Click on the following links for more details about the X‑TOLE2 and X‑TOLE3 clinical trials.

About Focal Onset Seizures

Epilepsy is a chronic neurological disorder, the hallmark of which is recurrent, unprovoked and unpredictable seizures. Individuals are diagnosed with epilepsy if they have two unprovoked seizures (or one unprovoked seizure with the likelihood of recurrent seizures) that were not caused by a known and reversible medical condition. Focal Onset Seizures (FOS) are the most common type of seizure experienced by people with epilepsy. FOS are localized within the brain and can either stay localized or spread to the entire brain, which is typically categorized as a secondarily generalized seizure. FOS account for approximately 60% of seizures in the U.S., which results in a total FOS patient population of approximately 1.8 million patients.

Addressing an Unmet Medical Need

Numerous ASMs are available for the treatment of seizures in the U.S. The treatment of an individual patient with FOS is currently focused on reduction of seizure frequency, with seizure freedom as the ultimate goal. Early treatment typically begins with monotherapy followed by increasing use of polypharmacy to manage patients with residual seizure burden. Despite the availability of multiple treatment options, up to 50% of patients are considered inadequately managed with initial lines of therapy warranting additional treatment options. For poorly managed patients, physicians increasingly turn to complementary mechanisms used as adjunctive therapy to control seizures. We believe there is a need for new, more effective and tolerable ASMs that have rapid onset of action, unique mechanisms important in polypharmacy, are easy to take (for example, once-daily), and durable.