XEN901 for Epilepsy


We are developing XEN901, a potent, highly selective Nav1.6 sodium channel inhibitor, for the treatment of epilepsy. By selectively targeting Nav1.6, it is anticipated that XEN901 may achieve efficacy conferred by this well-validated epilepsy target, but with a potentially improved therapeutic index compared with currently available non-selective sodium channel inhibitors.

There is strong human genetic validation supporting the rationale for treating epilepsy by blocking the Nav1.6 sodium channel. Nav1.6 is the most highly  expressed sodium channel in the excitatory pathways in the CNS. When mutations in the SCN8A gene, which encodes the Nav1.6 sodium channel, result in a gain of function in the Nav1.6 sodium channel, children can present with a very severe form of SCN8A Epileptic Encephalopathy, or SCN8A-EE, also known as EIEE13.

At the American Epilepsy Society (AES) Annual Meeting in December 2018, Xenon presented pre-clinical research related to XEN901 in a number of posters, which can be found on our “Publications” page under the XEN901 heading. 

Clinical Development


In February 2018, we initiated a randomized, double-blind, placebo-controlled Phase 1 clinical trial to evaluate XEN901’s safety, tolerability and PK in both SAD and MAD cohorts of healthy adult subjects.

We announced results from the XEN901 Phase 1 clinical trial and the related pilot TMS study at the AES Annual Meeting in December 2018 in a poster entitled “A First in Human Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics of a Novel Nav1.6 Selective Small Molecule Sodium Channel Inhibitor (XEN901) in Healthy Subjects.”

Based on pre-clinical results and the PK and safety profile demonstrated by XEN901 in the Phase 1 clinical trial, we are planning for Phase 2 development. Feedback from the FDA suggests that Xenon may be able to advance XEN901 directly into a Phase 2, or later stage, clinical trial examining efficacy in pediatric patients with SCN8A-EE, without requiring an adult clinical trial first.

We are currently in the process of completing a pediatric formulation of XEN901 and juvenile toxicology studies to support pediatric development activities. We intend to run a Phase 1 pharmacokinetic (PK) study in adults with the new pediatric formulation beginning late in the third quarter of this year, and then initiate a Phase 2/3 clinical trial in SCN8A-EE patients. More details about the final trial design, anticipated timing, criteria, and endpoints will be disclosed over the coming months..




About SCN8A Epilepsy

SCN8A Epileptic Encephalopathy (SCN8A-EE), also known as EIEE13, is a rare, extremely severe, single-gene epilepsy caused by mutations in the SCN8A gene that result in a gain-of-function in the Nav1.6 sodium channel. SCN8A-EE typically presents with seizure onset between birth and 18 months of age. Most children diagnosed with SCN8A-EE have seizures that can occur multiple times a day and are often difficult to treat. Other symptoms include learning difficulties, muscle spasms, low or high muscle tone, poor coordination, developmental delay, and features similar to autism. The extent of physical disability leaves some children able to make little or no voluntary movement. Most children will have trouble learning to speak, and some will need assistance from feeding tubes to get the nourishment they need to grow. It is also believed that children and teenagers with SCN8A-EE are at risk for Sudden Unexpected Death in Epilepsy (SUDEP).