Xenon Pharmaceuticals receives FDA feedback and plans to initiate XEN 496 phase III clinical trial for the treatment of KCNQ2-DEE before year-end.

Xenon Pharmaceuticals Inc. provided regulatory updates on its proprietary pediatric neurology program, XEN 496, a Kv7 potassium channel modulator that is a proprietary pediatric formulation of the active ingredient ezogabine being developed for the treatment of KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE). With the FDA having completed its review of the clinical trial protocol, Xenon is on track to initiate the XEN496 Phase III clinical trial in pediatric patients with KCNQ2-DEE before year-end. In addition, Xenon has received a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA), which recommends the granting of an orphan medicinal product designation for XEN 496 for the treatment of KCNQ2-DEE. This European designation is in addition to the FDA granting Fast Track designation for XEN 496 for the treatment of seizures associated with KCNQ2-DEE as well as Orphan Drug Designation (ODD) for the treatment of KCNQ2-DEE. The XEN496 Phase III “EPIK” clinical trial is titled “A Phase III Study of Adjunctive XEN 496 in Pediatric Subjects with KCNQ2 Developmental and Epileptic Encephalopathy.” This study is designed as a randomized, double-blind, placebo-controlled, parallel group, multicenter clinical trial to evaluate the efficacy, safety and tolerability of XEN 496 administered as adjunctive treatment in approximately 40 pediatric patients aged one month to less than 6 years with KCNQ2-DEE. After screening, patients will enter a baseline period to assess the frequency of seizures. Eligible subjects will be randomized on a 1:1 basis to receive either XEN 496 or placebo for approximately 15 weeks (titration and a 12-week maintenance period). At the end of treatment, there will be a period of tapering off of study drug, followed by a 28-day safety monitoring period. Patients may be considered for an open-label extension if they meet all requirements. The primary endpoint is the percent change from baseline in monthly countable motor seizure frequency during the blinded treatment period, as recorded by care givers in a daily seizure diary. Key secondary endpoints include the proportion of patients experiencing greater than or equal to 50 percent reduction in monthly seizure frequency from baseline, caregiver global impression of change (CaGI-C) scores, and caregiver global impression of severity (CaGI-S) scores. KCNQ2 epileptic encephalopathy (KCNQ2-EE), otherwise known as EIEE7, is a rare, severe neurodevelopmental disorder with a significant seizure burden and profound developmental impairment. KCNQ2-EE is uniquely characterized by multiple, daily, refractory seizures presenting within the first week of life with a prominent tonic component and autonomic signs.