Alixorexton Improves Cognition, Fatigue, and Disease Severity in Narcolepsy Type 1
KEY TAKEAWAYS
- Alixorexton was associated with improvements in disease severity, cognitive symptoms, and fatigue in narcolepsy type 1.
- Benefits were observed as early as 2 weeks and were sustained through the study period.
Treatment with alixorexton (Alkermes, Waltham, MA), an investigational oral orexin 2 receptor agonist, was associated with improvements in disease severity, cognitive symptoms, and fatigue in adults with narcolepsy type 1 (NT1), according to results from the phase 2 Vibrance-1 trial (NCT06358950) presented at the 2026 American Academy of Neurology (AAN) Annual Meeting. The findings address symptom domains that are often inadequately managed with currently available therapies.
In the randomized, placebo-controlled study, adults with NT1 received once-daily alixorexton (4 mg, 6 mg, or 8 mg) or placebo for 6 weeks, followed by an optional 7-week open-label extension, during which participants received alixorexton 6 mg (with dose adjustments permitted early in the extension). The study evaluated patient-reported outcomes, including disease severity, cognitive complaints, and fatigue, using validated scales such as the Narcolepsy Severity Scale–Clinical Trials (NSS-CT), British Columbia Cognitive Complaints Inventory (BC-CCI), and PROMIS-Fatigue.
Key Findings
- Alixorexton improved NSS-CT scores at week 6 across all dose groups (−9.1 [4 mg], −12.4 [6 mg], and −11.0 [8 mg] vs placebo; nominal P<.001), with benefits sustained through weeks 8 and 12.
- Cognitive symptoms improved, with significant reductions in BC-CCI scores observed as early as week 2 and maintained through the study period (nominal P<.0001 at week 6 vs placebo).
- Fatigue scores improved across all dose groups, with benefits seen by week 2 and sustained through week 6 and the extension phase (nominal P<.01 vs placebo).
- Patient-reported global assessments of cognition and fatigue showed similar improvement trends.
Source
Plazzi G. 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. Presented at: American Academy of Neurology Annual Meeting; April 18-22, 2026; Chicago, IL.