공지 • Apr 17
Alkermes plc Presents Additional Data from Vibrance-1 Phase 2 Study of Alixorexton in Patients with Narcolepsy Type 1
Alkermes plc announced plans to present new data from the Vibrance-1 phase 2 study evaluating alixorexton in patients with narcolepsy type 1 (NT1) at the American Academy of Neurology (AAN) 2026 Annual Meeting, taking place April 18-22, 2026 in Chicago. 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). Vibrance-1, a randomized, placebo-controlled, double-blind phase 2 study conducted in 92 patients with NT1, demonstrated clinically meaningful and statistically significant improvements from baseline compared to placebo in wakefulness, cognition, and fatigue. New data to be presented at AAN augment the detailed positive results from the six-week, randomized double-blind treatment (RDBT) period previously presented at the 2025 World Sleep Congress. The new data demonstrate clinically meaningful improvements from pre-treatment 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 seven-week open-label extension. More than 95% (n=88) of participants who entered Vibrance-1 completed treatment in both the six-week double-blind portion of the trial and the seven-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)1, British Columbia Cognitive Complaints Inventory (BC-CCI)2, Patient Global Impression of Severity (PGI-S) for Cognition3, PROMIS-Fatigue Short-form 6a (PROMIS-Fatigue)4, and PGI-S for Fatigue. 3 Clinically meaningful improvements were seen across all PRO measures at week 6 with alixorexton, with improvements sustained through weeks 12-13.5 Alixorexton was generally well tolerated across all doses tested throughout the six-week, RDBT period and the seven-week open-label extension period. No serious treatment-emergent adverse events (TEAEs) were reported. Most TEAEs were mild to moderate in severity. Details of the poster presentation are as follows: Poster Number: 14-002 Title: 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 Presenter: Giuseppe Plazzi, M.D., Ph.D., Neurologist, 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 Presentation Date: Monday, April 20, 2026 from 5:00 – 6:00 p.m. CT during Poster Session 6 About the Vibrance-1 Phase 2 Study (NCT06358950) Vibrance-1 was a phase 2, randomized, double-blind, dose-range-finding, placebo-controlled study evaluating the safety and efficacy of alixorexton in adults with narcolepsy type 1 (NT1). Participants (n=92) were randomized to receive one of three doses of alixorexton (4 mg, 6 mg or 8 mg) or placebo to be taken once-daily for six weeks. The primary endpoint assessed whether participants taking alixorexton experienced an improvement in wakefulness compared to participants taking placebo, as measured by the change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT) at week six. Secondary endpoints included change from baseline in Epworth Sleepiness Scale (ESS) score at week six, mean weekly cataplexy rate (WCR) at week six6, and incidence of adverse events. The study also included a number of exploratory patient-reported outcome measures, which evaluated the effect of alixorexton on participants’ disease severity, fatigue and cognition. All participants in the double-blind portion of the study were eligible to continue to a seven-week open-label safety extension portion of the study, followed by a long-term safety study. Alixorexton (formerly referred to as ALKS 2680) is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). Orexin, a neuropeptide produced in the lateral hypothalamus, is considered to be the master regulator of wakefulness due to its activation of multiple, downstream wake-promoting pathways that project widely throughout the brain.7 Targeting the orexin system may address excessive daytime sleepiness across hypersomnolence disorders, whether or not deficient orexin signaling is the underlying cause of disease.8 Once-daily oral administration of alixorexton was previously evaluated in a phase 1 study in healthy volunteers and patients with NT1, NT2 and IH, and in Vibrance-1 and Vibrance-2, phase 2 studies in patients with NT1 and NT2, respectively. Alixorexton is currently being evaluated in the phase 3 Brilliance Studies in patients with NT1 and NT2, and in the phase 2 Vibrance-3 study in patients with IH. Alixorexton has received Breakthrough Therapy designation for the treatment of NT1 from the U.S. Food and Drug Administration (FDA). 1 NSS-CT: 15-item self-administered questionnaire (score: 0-57) that assesses the severity and consequences of five major narcolepsy symptoms over the past 7 days: daytime sleepiness, cataplexy, hallucinations, sleep paralysis, and disturbed nighttime sleep. 2 BC-CCI: 6-item self-administered questionnaire (score: 0-18) assessing perceived problems with concentration, memory, expressing thoughts, word finding, slow thinking, and difficulty solving problems over the past 7 days (=4 = normative). 3 PGI-S for Cognition, Fatigue: Self-administered, single items assessing cognitive impairment as well as fatigue, over the past 7 days on a 5-point scale (none, mild, moderate, severe or very severe). 4 PROMIS-Fatigue: 6-item self-administered questionnaire assessing the severity of a patient’s fatigue over the past 7 days. Items are scored and transformed to T-scores (5 Per protocol, select PROs were administered at week 12 (NSS-CT, BC-CCI) while others were administered at week 13. 6 Weekly cataplexy rate was derived at Week 6 from patients’ cataplexy diaries over Weeks 5 and 6. 7 Buysse, D. Diagnosis and assessment of sleep and circadian rhythm disorders. Journal of Psychiatric Practice. 2005; 11(2):102-115 8 Ten-Blanco M, Flores A, Cristino L, Pereda-Perez I. Targeting the orexin/hypocretin system for the treatment of neuropsychiatric and neurodegenerative diseases: From animal to clinical studies. Frontiers in Neuroendocrinology. 2023;69(101066).