Dublin — Alkermes plc said detailed results from its Phase 2 Vibrance-2 study showed that alixorexton improved wakefulness and excessive daytime sleepiness in adults with narcolepsy type 2.
The company presented the data at SLEEP 2026, the 40th annual meeting of the Associated Professional Sleep Societies, held June 14-17 in Baltimore.
Alixorexton is an investigational, once-daily oral orexin 2 receptor agonist being developed for narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia. Alkermes said the Vibrance-2 study is the first large Phase 2 trial of an orexin 2 receptor agonist to show clinically meaningful and statistically significant improvements in wakefulness and excessive daytime sleepiness compared with placebo in patients with narcolepsy type 2.
The randomized, double-blind, dose-ranging study evaluated alixorexton in 93 adults with narcolepsy type 2. The drug met the study’s dual primary endpoints, showing statistically significant and clinically meaningful improvements from baseline compared with placebo on the Maintenance of Wakefulness Test and the Epworth Sleepiness Scale at week eight.
Patient-reported improvements in wakefulness were sustained through a five-week open-label extension period. The company said alixorexton also showed clinically meaningful improvements in exploratory patient-reported measures of fatigue and cognition.
“The Vibrance-2 results presented at SLEEP provide compelling evidence that alixorexton meaningfully improved measures of wakefulness, fatigue and cognition in patients with narcolepsy type 2. As excitement builds around innovative, potential new treatments, these findings are particularly notable as the first orexin 2 receptor agonist to demonstrate such clinically meaningful benefits in patients with narcolepsy type 2, a population without known orexin deficiency,” said Richard K. Bogan, M.D., FCCP, FAASM, Principal of Bogan Sleep Consultants, LLC and Associate Clinical Professor at the University of South Carolina School of Medicine. “Alongside positive Vibrance-1 data in narcolepsy type 1, these results underscore alixorexton’s potential to become an important new treatment option for patients with narcolepsy.”
In the study, alixorexton demonstrated clinically meaningful improvements in mean sleep latency on the Maintenance of Wakefulness Test at week eight across all doses tested. The 14 mg and 18 mg doses achieved statistical significance based on the pre-specified analysis, with p-values of 0.049 and 0.047, respectively.
Participants had a mean sleep latency of about six minutes at baseline. At week eight, observed mean sleep latencies were about 16 minutes for the 10 mg dose and about 14 minutes for both the 14 mg and 18 mg doses.
On the Epworth Sleepiness Scale, alixorexton showed clinically meaningful improvements in excessive daytime sleepiness across all doses tested at week eight. The 18 mg dose achieved statistical significance, with a p-value of 0.046, based on the pre-specified analysis.
At baseline, participants had a mean Epworth Sleepiness Scale score of about 17, reflecting severe excessive daytime sleepiness. By week eight, most participants receiving alixorexton across all dose groups reported normal or mild excessive daytime sleepiness. At week 13, mean scores across all dose groups were within the normal range.
Alkermes said the study also showed clinically meaningful improvements in exploratory patient-reported outcomes measuring fatigue and cognition. On the PROMIS-Fatigue measure, alixorexton showed clinically meaningful improvements from baseline compared with placebo at week eight across all doses tested, with p-values of 0.044 and 0.001 for the 14 mg and 18 mg doses, respectively. Improvements were seen as early as week two and continued through week 13.
On the British Columbia Cognitive Complaints Inventory, alixorexton showed clinically meaningful improvements in the severity of cognitive impairment compared with placebo at week eight across all doses tested, with a p-value of 0.042 for the 18 mg dose. Improvements were also observed as early as week two and continued through week 13.
Alixorexton was generally well tolerated at all doses tested during the eight-week randomized treatment period and the five-week open-label extension. No serious treatment-emergent adverse events were reported. The company said no safety signals were observed in hepatic or renal parameters, vital signs or ECGs, and no treatment-related clinically meaningful changes were observed on ophthalmic exams.
Most treatment-emergent adverse events were mild to moderate. The most common events in patients treated with alixorexton were pollakiuria, insomnia, micturition urgency, dizziness and headache.
More than 95 percent of participants completed treatment during the eight-week randomized period, and nearly 90 percent completed the 13-week open-label extension study.
“People living with narcolepsy type 2 frequently experience a lengthy and challenging diagnostic journey, and many continue to live with significant symptom burden following diagnosis. The Vibrance-2 dataset reinforces our belief that alixorexton has the potential to deliver clinically meaningful benefits across key symptoms. Alkermes is committed to researching potential new medicines with the goal of advancing care for people living with central disorders of hypersomnolence,” said Craig Hopkinson, M.D. (MBChB), Chief Medical Officer and Executive Vice President, Research & Development at Alkermes.
Based on positive results from its Phase 2 Vibrance studies, Alkermes has started a global Phase 3 program evaluating once-daily and split-dose regimens of alixorexton in patients with narcolepsy type 1 and narcolepsy type 2.
The Vibrance-2 trial was a Phase 2 randomized, double-blind, dose-range-finding, placebo-controlled study evaluating alixorexton, formerly known as ALKS 2680, in adults with narcolepsy type 2. Participants were randomized to receive alixorexton at 10 mg, 14 mg or 18 mg, or placebo, once daily for eight weeks.
