Azetukalner
An investigational treatment for Focal Epilepsy.
The same compound appears under different names depending on the context. Here is how to identify Azetukalner wherever you encounter it, plus the key facts at a glance.
- Generic name
- Azetukalner
- Development code
- XEN1101
- Drug class
- Ion channel modulator (Kv7 activator)
- Manufacturer
- Xenon Pharmaceuticals
- How it's taken
- Taken by mouth once daily with food, as add-on therapy on top of a patient's existing seizure medicines.
An investigational once-daily Kv7 potassium-channel opener from Xenon Pharmaceuticals, the same mechanism class as opakalim. It is the most advanced Kv7 program in epilepsy, with a positive Phase 3 focal-seizure study reported in 2026 and an FDA application submitted in September 2026.
Where Azetukalner fits
An investigational once-daily Kv7 opener positioned for patients not adequately controlled on existing mechanisms, the same target class as opakalim, and the most advanced Kv7 program, with positive Phase 3 focal-seizure data in 2026.
How Azetukalner works
Like opakalim, azetukalner turns on Kv7 potassium channels, the natural 'off switch' on nerve cells. When these channels open, potassium flows out and the cell settles down, making it harder to fire the runaway bursts that start a focal seizure. Azetukalner targets the Kv7.2 and Kv7.3 channels most relevant to seizure control.
This is the same validated target that the withdrawn drug ezogabine (Potiga) proved could work in epilepsy. Azetukalner and opakalim are the two leading efforts to deliver that benefit with a cleaner, more selective molecule that avoids ezogabine's tolerability problems[2].
Mechanism: Selective Kv7.2/7.3 potassium channel opener that stabilizes neuronal membranes and reduces excessive firing
Side effects and safety
In clinical trials, the most common side effects have been dizziness, sleepiness, headache, and fatigue, generally mild to moderate. Importantly, no retinal or skin-pigmentation problems of the kind that led to ezogabine's withdrawal have been reported.
Because azetukalner is still investigational, its complete safety profile, including any rare risks, will be defined by the full Phase 3 data and, ultimately, the FDA label if it is approved[2].
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Azetukalner
Taken by mouth once daily with food, as add-on therapy on top of a patient's existing seizure medicines. The pivotal Phase 3 studies tested 15 mg and 25 mg once-daily doses. Outside of a clinical trial, azetukalner is not yet available[3].
Clinical trial results
In the Phase 3 X-TOLE2 study (NCT05614063), azetukalner significantly reduced monthly focal-seizure frequency in adults with highly treatment-resistant epilepsy (a median of 5 prior seizure medicines). Topline results reported in March 2026 showed a median reduction of about 53% at the 25 mg dose versus roughly 10% for placebo, a placebo-adjusted improvement of about 43%[1].
A second focal-seizure Phase 3 study, X-TOLE3 (NCT05716100), is ongoing, along with a Phase 3 study in primary generalized tonic-clonic seizures. Xenon announced on September 17, 2026 that it had submitted a New Drug Application to the FDA for focal seizures[5][4].
Main registered trial: NCT05614063 on ClinicalTrials.gov. Check it for the current status, sites and contacts before asking about enrollment.
Development history
Azetukalner (development code XEN1101) was developed by Xenon Pharmaceuticals, a company focused on ion-channel drugs. After a positive Phase 2b study (X-TOLE) established the drug's promise, Xenon advanced it into a broad Phase 3 program across multiple seizure types. The positive X-TOLE2 readout in 2026 positioned azetukalner as the most advanced Kv7 activator in epilepsy and a direct benchmark for opakalim[1][2].
Explore Focal Epilepsy trials
Other Focal Epilepsy treatments
Azetukalner and opakalim (BHV-7000) are the two leading Kv7 potassium-channel openers in late-stage epilepsy development, both aiming to revive a mechanism validated by ezogabine (Potiga) but without its retinal and skin-pigmentation liabilities. Azetukalner is further along, with positive Phase 3 focal-seizure data reported in early 2026 and an FDA filing planned, whereas opakalim's pivotal readouts (RISE 2 and RISE 3) are expected in the second half of 2026. Both would compete in a crowded adjunctive market led on efficacy by cenobamate (Xcopri).
Common questions about Azetukalner
▸What is Azetukalner?
An investigational once-daily Kv7 potassium-channel opener from Xenon Pharmaceuticals, the same mechanism class as opakalim. It is the most advanced Kv7 program in epilepsy, with a positive Phase 3 focal-seizure study reported in 2026 and an FDA application submitted in September 2026.
▸How does Azetukalner work?
Like opakalim, azetukalner turns on Kv7 potassium channels, the natural 'off switch' on nerve cells. When these channels open, potassium flows out and the cell settles down, making it harder to fire the runaway bursts that start a focal seizure. Azetukalner targets the Kv7.2 and Kv7.3 channels most relevant to seizure control.
This is the same validated target that the withdrawn drug ezogabine (Potiga) proved could work in epilepsy. Azetukalner and opakalim are the two leading efforts to deliver that benefit with a cleaner, more selective molecule that avoids ezogabine's tolerability problems[2].
▸What are the side effects of Azetukalner?
In clinical trials, the most common side effects have been dizziness, sleepiness, headache, and fatigue, generally mild to moderate. Importantly, no retinal or skin-pigmentation problems of the kind that led to ezogabine's withdrawal have been reported.
Because azetukalner is still investigational, its complete safety profile, including any rare risks, will be defined by the full Phase 3 data and, ultimately, the FDA label if it is approved[2].
▸How is Azetukalner taken?
Taken by mouth once daily with food, as add-on therapy on top of a patient's existing seizure medicines. The pivotal Phase 3 studies tested 15 mg and 25 mg once-daily doses. Outside of a clinical trial, azetukalner is not yet available[3].
▸Is Azetukalner FDA approved?
Azetukalner is currently in phase 3 clinical trials for Focal Epilepsy. It has not yet received FDA approval.
▸What is azetukalner used for?
▸Is azetukalner FDA approved?
▸What did the azetukalner X-TOLE2 trial show?
In the Phase 3 X-TOLE2 study (NCT05614063), azetukalner significantly reduced monthly focal-seizure frequency in adults who had tried a median of 5 prior seizure medicines. Topline results reported in March 2026 showed a median seizure reduction of about 53% at the 25 mg dose versus roughly 10% for placebo, a placebo-adjusted improvement of about 43%. [1]
▸What are the side effects of azetukalner?
In clinical trials, the most common side effects of azetukalner have been dizziness, sleepiness, headache, and fatigue, generally mild to moderate. No retinal or skin-pigmentation problems of the kind that led to ezogabine's withdrawal have been reported. Because azetukalner is still investigational, its complete safety profile will be defined by the full Phase 3 data and any eventual FDA label. [2]
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Xenon Pharmaceuticals (GlobeNewswire) · March 2026. Xenon Announces Positive Topline Data from Phase 3 X-TOLE2 Study of Azetukalner in Focal Onset Seizures (FOS). https://www.globenewswire.com/news-release/2026/03/09/3251686/33485/en/xenon-announces-positive-topline-data-from-phase-3-x-tole2-study-of-azetukalner-in-focal-onset-seizures-fos.html
- NeurologyLive. Phase 3 X-TOLE2 Data Support NDA Submission for Azetukalner in Focal Onset Seizures. https://www.neurologylive.com/view/phase-3-x-tole2-data-support-nda-submission-azetukalner-focal-onset-seizures
- U.S. National Library of Medicine, ClinicalTrials.gov. A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE2). https://clinicaltrials.gov/study/NCT05614063
- U.S. National Library of Medicine, ClinicalTrials.gov. A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3). https://clinicaltrials.gov/study/NCT05716100
- Xenon Pharmaceuticals · 2026-09-17. Xenon Announces Azetukalner NDA Submission to FDA for Focal Seizures and Provides Update on Psychiatry Clinical Program. https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-announces-azetukalner-nda-submission-fda-focal-seizures