Xenon Pharmaceuticals Inc. (Nasdaq: XENE) has announced advancements in its azetukalner program for epilepsy and major depressive disorder (MDD), along with progress in its early-stage pipeline of ion channel modulators. The company anticipates topline data from the X-TOLE2 Phase 3 study in focal onset seizures (FOS) in the second half of 2025 and plans to initiate the X-NOVA2 Phase 3 trial in MDD by year-end.
Azetukalner Clinical Development
Azetukalner, a novel, highly potent, selective Kv7 potassium channel opener, is Xenon's lead molecule. It is currently in Phase 3 development for epilepsy, including focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS), and is being explored for MDD and other neuropsychiatric disorders.
The Phase 3 FOS studies are ongoing, with the X-TOLE2 topline data readout expected in the second half of 2025. These trials are multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy, safety, and tolerability of azetukalner in patients with FOS. The X-ACKT Phase 3 study, currently enrolling patients, is designed to support regulatory submissions for PGTCS. This trial is also multicenter, randomized, double-blind, and placebo-controlled, assessing the efficacy, safety, and tolerability of azetukalner in patients with PGTCS.
Xenon continues to generate long-term data on azetukalner's efficacy and safety through the X-TOLE open-label extension (OLE) study, with over 600 patient-years of drug exposure to date. New 36-month data from the OLE study in FOS will be presented at the American Epilepsy Society (AES) annual meeting next month.
MDD Program Expansion
Xenon is expanding azetukalner's potential into MDD, with the X-NOVA2 Phase 3 clinical trial expected to begin before the end of the year. This trial is the first of three Phase 3 studies evaluating azetukalner in patients with MDD.
An investigator-sponsored Phase 2 proof-of-concept study of azetukalner in MDD, led by the Icahn School of Medicine at Mount Sinai, has completed patient enrollment, with results anticipated in the first half of 2025.
Early-Stage Pipeline
Xenon is advancing multiple candidates towards IND filings in 2025, targeting Kv7, Nav1.7, and Nav1.1. IND-enabling work is underway with multiple Kv7 development candidates, which may have utility in seizures, pain, and neuropsychiatric disorders like MDD. A lead Nav1.7 development candidate is also in IND-enabling studies, targeting pain. The company expects to nominate a lead candidate within its Nav1.1 program in 2025, potentially addressing Dravet Syndrome.
Financial Status
As of September 30, 2024, Xenon's cash, cash equivalents, and marketable securities totaled $803.3 million. The company anticipates sufficient cash to fund operations into 2027, including the completion of the azetukalner Phase 3 epilepsy studies and late-stage clinical development in MDD.
Analyst Perspective
Analysts project that azetukalner has the potential to achieve blockbuster status within 3-5 years post-launch, with some estimating over $1 billion in sales in the epilepsy market alone. The expansion into the MDD market, estimated at around $700 million, adds another layer of potential value to Xenon's portfolio.
