Name: Azetukalner (XEN1101) in Focal onset seizures: Pharmacodynamics
Published: 2026-09-21T21:41:53-04:00

Product information and disease description Product description Product information Pharmacology

Pharmacodynamics

5 evidence topics · 5 sources

Preclinical antiseizure activity in rodent seizure models

“In the MES test, azetukalner has ED50 values of 1.1 mg/kg in rats at 60 min after per os (p.o.) dosing, and 2.2 mg/kg in mice at 120 min after i.p. dosing. In mice, azetukalner is also effective in protecting against seizures induced by subcutaneous (s.c.) pentylenetetrazole, s.c. picrotoxin, s.c. bicuculline, and 6 Hz stimulation, with ED50 values < 10 mg/kg i.p., which correspond to a > 3–19-fold greater potency compared with ezogabine (Table 2 )” (opens the source at this quote in a new tab)

Transcranial magnetic stimulation biomarkers of cortical excitability

“Consistent with previous TMS investigations of antiepileptic drugs (AEDs) targeting ion channels, the amplitude of TEPs occurring at early (15–55 msec after TMS) and at late (150–250 msec after TMS) latencies were significantly suppressed from baseline by 20 mg of XEN1101. Furthermore, the RMT showed a significant time-dependent increase that correlated with the XEN1101 plasma concentration.” (opens the source at this quote in a new tab)

Concentration-effect relationship for resting motor threshold

“Mean plasma azetukalner concentrations (± SD) at 2, 4, and 6 h after dosing were 15.7 ± 21.5 ng/mL, 30.2 ± 21.9 ng/mL, and 42.1 ± 19.1 ng/mL, respectively. At the time of individual peak drug concentrations, plasma azetukalner levels correlated significantly with changes in RMTs, but not with changes in TEPs.” (opens the source at this quote in a new tab)

Use of the transcranial magnetic stimulation study for target engagement and dose selection

“In addition, data from a Phase 1b transcranial magnetic stimulation, or TMS, study – which was designed to assess azetukalner’s ability and potency to modulate cortical excitability – demonstrated activity in the target central nervous system, or CNS, tissue and helped inform dose selection for our Phase 2b clinical study.” (opens the source at this quote in a new tab)

In vivo additive effects with other antiseizure medications

“Additionally, a new poster highlighting the mechanistic characterization of azetukalner will also be presented, including KV7 binding, enhanced channel opening, and rational polytherapy potential. This poster will include in vivo data demonstrating the potential additive effects of azetukalner when used in combination with commonly prescribed antiseizure medications (ASMs), reinforcing its opportunity to enhance seizure control through the application of rational polytherapy in clinical practice.” (opens the source at this quote in a new tab)