New AAN Poster Presentation on Alixorexton for Narcolepsy Type 1: Improvement in Disease Severity, Cognitive Functioning, and Fatigue

CONFERENCE REPORTER

In a poster presentation at the American Academy of Neurology (AAN) 2026 Annual Meeting, investigators presented additional data from the Vibrance-1 phase 2 study of alixorexton in patients with narcolepsy type 1 (NT1). According to the results, participants with NT1 taking once-daily alixorexton demonstrated nominally significant, clinically meaningful improvements in patient-reported disease severity, cognitive impairment, and fatigue, with improvements sustained through 12 to 13 weeks.¹

Alixorexton is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of NT1, narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH).

“The Vibrance‑1 data suggest that alixorexton may offer meaningful symptom improvement for people living with narcolepsy type 1 by addressing wakefulness, cataplexy, cognition, and fatigue—symptoms that profoundly affect daily functioning. Psychiatric and neuropsychiatric colleagues should be encouraged by the consistent improvements seen across patient‑reported outcomes, alongside a manageable safety profile and high treatment completion. These findings reinforce the therapeutic potential of orexin 2 receptor agonists, with upcoming phase 3 studies representing the critical next step to further establish alixorexton’s clinical profile," Rafael del Río Víllegas, MD, PhD, the team leader of the Neurophysiology and Sleep Disorders Unit at Vithas Madrid La Milagrosa University Hospital, and study presenter, exclusively told Psychiatric Times.

Vibrance-1 was a randomized, placebo-controlled, double-blind phase 2 study conducted in 92 participants with NT1. These new data presented at AAN augment the detailed positive results from the 6-week, randomized double-blind treatment period previously presented at the 2025 World Sleep Congress. The new data demonstrate clinically meaningful improvements from pretreatment baseline on established measures evaluating excessive daytime sleepiness and cataplexy, as well as participant-reported outcomes, including narcolepsy symptom severity, cognitive functioning and fatigue in patients with NT1 through the 7-week open-label extension. More than 95% (n=88) of participants who entered Vibrance-1 completed treatment in both the 6-week double-blind portion of the trial and the 7-week open-label extension for a total of 13 weeks. Exploratory patient-reported outcomes (PROs) in Vibrance-1 included the Narcolepsy Severity Scale-Clinical Trials (NSS-CT), British Columbia Cognitive Complaints Inventory (BC-CCI)2, Patient Global Impression of Severity (PGI-S) for Cognition, PROMIS-Fatigue Short-form 6a (PROMIS-Fatigue), and PGI-S for Fatigue. Clinically meaningful improvements were seen across all PRO measures at week 6 with alixorexton, with improvements sustained through weeks 12 and 13.

Participants were randomly assigned to placebo (n=23) or alixorexton (4 mg, n=23; 6 mg, n=22; 8 mg, n=24); 88 completed OLE treatment. For all alixorexton groups, improvements from baseline on NSS-CT were seen at week 6 (4 mg, −9.1; 6 mg, −12.4; 8 mg, −11.0; all nominal P<0.001 vs placebo), week 8, and week 12. Improvements on BC-CCI from baseline were seen at week 2, week 6 (all nominal P<0.0001 vs placebo at week 6) and through the OLE for all alixorexton groups. A similar trend was seen on PGI-S Cognition. All alixorexton groups reported improved scores on PROMIS-Fatigue at week 2 that were sustained through week 6 (all nominal P<0.01 vs placebo) and the OLE. A similar trend was seen on PGI-S Fatigue.

“Results from the Vibrance-1 phase 2 study of alixorexton provide a rich and comprehensive dataset that allows us to better understand its treatment effects on core symptoms of narcolepsy type 1. Improvements observed at week 6 across patient-reported measures of disease severity, cognitive functioning and fatigue were sustained through the seven-week open-label extension, supporting the durability of alixorexton’s effects,” said Giuseppe Plazzi, MD, PhD, a neurologist, director of the Narcolepsy Center at the IRCCS of the Neurological Sciences of Bologna, and a professor of childhood neuropsychiatry at the University of Modena and Reggio Emilia. “These patient-reported outcomes highlight clinically relevant dimensions of narcolepsy that are often underrecognized, yet central to patients’ daily functioning, and demonstrate alixorexton’s potential to make a meaningful impact for people living with narcolepsy type 1.”

Alixorexton was generally well tolerated across all doses tested throughout the 6-week, RDBT period and the 7-week open-label extension period. No serious treatment-emergent adverse events (TEAEs) were reported. Most TEAEs were mild to moderate in severity.

These data will bolster the recently-initiated Brilliance Studies, a phase 3 program evaluating the safety and efficacy of alixorexton compared with placebo in adults with NT1 and NT2.²

“The breadth and depth of the data generated in the Vibrance-1 study provide strong evidence of alixorexton’s potential to meaningfully impact the lives of patients by addressing multiple elements across the spectrum of disease burden of narcolepsy type 1. Importantly, the differentiated profile observed across patient-reported symptom severity, cognition and fatigue highlights alixorexton’s potential to offer a distinct and clinically relevant approach for patients with narcolepsy,” said Craig Hopkinson, MD, MBChB, the chief medical officer and executive vice president of research & development at Alkermes. “These data provide a strong foundation for our phase 3 program and reinforce our confidence as we enroll the recently initiated Brilliance Studies in narcolepsy type 1 and type 2. We look forward to further characterizing alixorexton’s efficacy and safety profile in these pivotal trials.”

References

1. Dauvilliers Y, Grunstein RR, Mignot E, et al. Improvement in patient-reported disease severity, cognitive functioning, and fatigue in patients with narcolepsy type 1 treated with alixorexton, an orexin 2 receptor agonist, in the Vibrance-1 phase 2 study. Poster presented at: American Academy of Neurology 2026 Annual Meeting; April 18-22, 2015; Chicago, IL. Accessed April 20, 2026. https://www.aan.com/msa/Public/Events/AbstractDetails/63931

2. Kuntz L. Phase 3 Brilliance studies initiated on alixorexton for the treatment of narcolepsy type 1 and type 2. Psychiatric Times. April 1, 2026. https://www.psychiatrictimes.com/view/phase-3-brilliance-studies-initiated-on-alixorexton-for-the-treatment-of-narcolepsy-type-1-and-type-2