As reported on Business Wire, Alkermes plc has initiated a global phase 3 clinical development program to evaluate alixorexton, an investigational oral therapy for people living with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). The late-stage program, known collectively as the Brilliance Studies, is designed to assess both the efficacy and safety of alixorexton compared with placebo in adult patients.
Alixorexton is a selective orexin 2 receptor agonist, a mechanism intended to directly address the underlying orexin signaling deficits associated with narcolepsy. In addition to NT1 and NT2, the compound is also being developed for idiopathic hypersomnia.
Overview of the Brilliance Phase 3 Program
The Brilliance program includes three randomized, double-blind, placebo-controlled trials, each lasting 12 weeks, and explores both once-daily and split-dose administration strategies. Two studies focus on NT1 (Brilliance NT1 Studies 302 and 304), while one study is dedicated to NT2 (Brilliance NT2 Study 303). Collectively, the trials are enrolling patients across North America, Europe, and the Asia-Pacific region.
Study Designs and Endpoints
The two NT1 trials will each enroll approximately 150 participants, who will be randomized to receive one of two alixorexton dosing regimens or placebo. The primary outcome measure in both studies is change in wakefulness, assessed via mean sleep latency on the Maintenance of Wakefulness Test (MWT). Key secondary outcomes include changes in daytime sleepiness measured by the Epworth Sleepiness Scale (ESS), reductions in weekly cataplexy episodes, patient-reported measures of fatigue and cognitive function, overall disease severity, and safety outcomes.
The NT2 study plans to enroll about 180 participants, who will receive one of three dosing regimens of alixorexton or placebo. As with the NT1 trials, the primary endpoint is improvement in wakefulness as measured by the MWT. Secondary assessments include ESS score changes, patient-reported outcomes related to daily functioning, and adverse event monitoring.
Path Forward
According to Alkermes’ leadership, the phase 3 launch builds on encouraging results from a previously completed phase 2 program in both narcolepsy subtypes. The company aims to use the Brilliance studies to refine dosing flexibility while further defining the benefit–risk profile of alixorexton.
Patients who complete a Brilliance trial will be eligible to roll over into a long-term, open-label extension study focused on safety. Additional trial details are available through ClinicalTrials.gov and the Brilliance Studies website for U.S. audiences.
