DUBLIN — Alkermes plc said data from its Phase 2 Vibrance-1 study of alixorexton in adults with narcolepsy type 1 have been published in The Lancet Neurology, showing significant improvements in wakefulness, daytime sleepiness and other symptoms of the disorder.
Alixorexton is an investigational oral, selective orexin 2 receptor agonist being developed for narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia. Alkermes has begun a global Phase 3 program, known as the Brilliance Studies, evaluating once-daily and split-dose regimens in adults with narcolepsy types 1 and 2.
The Vibrance-1 study enrolled 92 adults with narcolepsy type 1 and included a six-week randomized, placebo-controlled, double-blind treatment period followed by an optional seven-week open-label extension.
Treatment with once-daily alixorexton resulted in statistically significant improvements compared with placebo in objective and subjective measures of excessive daytime sleepiness, including the Maintenance of Wakefulness Test and Epworth Sleepiness Scale.
All three doses tested — 4 mg, 6 mg and 8 mg — produced mean sleep latency values within the normative range on the Maintenance of Wakefulness Test and Epworth Sleepiness Scale at week six. The weekly cataplexy rate was also significantly reduced compared with placebo in the 6 mg group.
Alixorexton also produced clinically meaningful improvements in exploratory patient-reported measures of overall disease severity, fatigue, cognition and health-related quality of life, according to Alkermes.
The drug was generally well tolerated across all doses, with most treatment-emergent adverse events classified as mild to moderate. No serious treatment-emergent adverse events were reported.
“The data published in The Lancet Neurology highlight the robust efficacy of once-daily doses of alixorexton in patients with narcolepsy type 1 across measures of wakefulness and excessive daytime sleepiness. Along with a generally well-tolerated profile, alixorexton demonstrated improvements across a broad range of symptoms that affect daily functioning, including cataplexy, overall disease severity, cognition and fatigue,” said Giuseppe Plazzi, M.D., Ph.D., Neurologist and Director of the Narcolepsy Center at the IRCCS of the Neurological Sciences of Bologna and Professor of Childhood Neuropsychiatry at the University of Modena and Reggio Emilia.
“These data are a substantial contribution to the evidence base supporting the potential of orexin 2 receptor agonists to transform the treatment of narcolepsy and the utility of a range of doses to address the individual needs of people living with NT1,” Plazzi said.
Craig Hopkinson, M.D. (MBChB), Chief Medical Officer and Executive Vice President, Research & Development at Alkermes, said the Vibrance program has increased the company’s confidence in the drug’s potential.
“In the Vibrance-1 study, alixorexton demonstrated substantial and clinically meaningful benefits across multiple dimensions of narcolepsy type 1,” Hopkinson said. “The totality of evidence generated across the Vibrance phase 2 program in narcolepsy has reinforced our confidence in alixorexton’s potential to meaningfully impact the lives of people living with narcolepsy type 1 and type 2.”
The Phase 2 Vibrance-1 study, NCT06358950, was designed to evaluate the safety and efficacy of alixorexton in adults with narcolepsy type 1. Participants were randomized to receive 4 mg, 6 mg or 8 mg of alixorexton or placebo once daily for six weeks.
The primary endpoint measured changes in wakefulness using the Maintenance of Wakefulness Test. Secondary endpoints included changes in Epworth Sleepiness Scale scores, weekly cataplexy rates and adverse events. Participants could continue into a seven-week open-label safety extension followed by a long-term safety study.
