alixorexton (ALKS 2680) / Alkermes - LARVOL DELTA

Safety, tolerability, and efficacy of alixorexton, a selective orexin 2 receptor agonist for narcolepsy type 1 (Vibrance-1): a randomised, double-blind, placebo-controlled, phase 2 trial. (PubMed, Lancet Neurol) - P2 | "In this phase 2 trial, once-daily oral alixorexton provided clinically meaningful improvements at 6 weeks for participants with narcolepsy type 1, including in wakefulness, excessive daytime sleepiness, and cataplexy. The treatment was generally well tolerated, with adverse events consistent with the known on-target effects of OX2R agonists. Together, these findings support the further phase 3 evaluation of alixorexton as a potential therapeutic option for people with narcolepsy type 1."

Journal • P2 data • Cataplexy • CNS Disorders • Dermatology • Excessive Daytime Sleepiness • Insomnia • Narcolepsy • Sleep Disorder

Targeting Orexin 2 Receptors in Idiopathic Hypersomnia and Narcolepsy: A Randomised Phase 1b Proof-Of-Concept Study of Alixorexton. (PubMed, J Sleep Res) - "These findings support OX2R agonism as a therapeutic approach for central disorders of hypersomnolence, including conditions with uncertain orexin dysfunction and informed ongoing phase 2 evaluation in IH and narcolepsy. Trial Registration: A study in healthy subjects to see the effects of the test medicine ALKS 2680 in single- and multi-dose regimen; prospectively registered at ISRCTN on October 17, 2022 (identifier: ISRCTN98204977; URL: https://www.isrctn.com/ISRCTN98204977)."

Journal • P1 data • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Vibrance-3: A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Idiopathic Hypersomnia (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: Alkermes, Inc. | N=96 ➔ 126 | Trial completion date: Jun 2026 ➔ Nov 2026 | Trial primary completion date: Jun 2026 ➔ Nov 2026

Enrollment change • Trial completion date • Trial primary completion date • Sleep Disorder

ALKS 2680-203: A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Idiopathic Hypersomnia (clinicaltrialsregister.eu) - P1/2 | N=55 | Active, not recruiting | Sponsor: Alkermes Inc. | N=28 ➔ 55 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Sleep Disorder

ALKS 2680-203: A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Idiopathic Hypersomnia (clinicaltrialsregister.eu) - P1/2 | N=28 | Recruiting | Sponsor: Alkermes Inc. | N=15 ➔ 28

Enrollment change • Sleep Disorder

Alkermes Announces Orphan Drug Designations for Alixorexton in the U.S. and Europe (Businesswire) - "Alixorexton is currently being evaluated in the phase 3 Brilliance Studies in adults with NT1 and NT2, and in the phase 2 Vibrance-3 study in adults with IH (Brilliance NT1 – Study 302: NCT07455383; Brilliance NT2 – Study 303: NCT07502443; Brilliance NT1 – Study 304: NCT07540897; Vibrance-3: NCT06843590)."

Orphan drug • CNS Disorders • Narcolepsy

Alixorexton Granted Breakthrough Therapy Designation by U.S. FDA for the Treatment of Narcolepsy Type 1 (Alkermes Press Release) - "The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to alixorexton for the treatment of narcolepsy type 1 (NT1), based on phase 1 and phase 2 clinical data, including positive results from Vibrance-1, a large (n=92) phase 2 study evaluating alixorexton in patients with NT1...Alkermes plans to initiate the alixorexton narcolepsy global phase 3 program in the first quarter of 2026."

Breakthrough therapy • New P3 trial • Narcolepsy

On June 11, 2026, Alkermes plc has been awarded orphan drug designation by the US FDA for its investigational drug alixorexton, aimed at treating idiopathic hypersomnia (Gurufocus) - "This oral orexin 2 receptor agonist is currently undergoing phase 2 clinical trials."

Orphan drug • CNS Disorders • Sleep Disorder

ALKS 2680-302: A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1 (clinicaltrialsregister.eu) - P2/3 | N=75 | Not yet recruiting | Sponsor: Alkermes Inc.

New P2/3 trial • Narcolepsy • Sleep Disorder

ALKS 2680-303: A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 2 (clinicaltrialsregister.eu) - P2/3 | N=65 | Not yet recruiting | Sponsor: Alkermes Inc.

New P2/3 trial • Narcolepsy • Sleep Disorder

ALKS 2680-302: A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1 (clinicaltrialsregister.eu) - P2/3 | N=56 | Not yet recruiting | Sponsor: Alkermes Inc.

New P2/3 trial • Narcolepsy • Sleep Disorder

A Study to Evaluate the Efficacy, Safety and Tolerability of ALKS 2680 in Adults With Narcolepsy Type 1 (Brilliance NT1 - 304) (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Alkermes, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Narcolepsy • Sleep Disorder

Improvement in Patient-reported Disease Severity, Cognitive Functioning, and Fatigue in Patients With Narcolepsy Type One Treated With Alixorexton, an Orexin Two Receptor Agonist, in the Vibrance-1 Phase Two Study (AAN 2026) - P2 | "A similar trend was seen on PGI-S Fatigue. Conclusions In patients with NT1, once-daily alixorexton demonstrated nominally significant, clinically meaningful improvements in patient-reported disease severity, cognitive impairment and fatigue, with improvements sustained through 12-13 weeks."

Clinical • Alzheimer's Disease • Cataplexy • Cognitive Disorders • Excessive Daytime Sleepiness • Fatigue • Narcolepsy • Sleep Disorder

Brilliance NT1: A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Alkermes, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Narcolepsy • Sleep Disorder

Brilliance NT2: A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 2 (clinicaltrials.gov) - P3 | N=176 | Recruiting | Sponsor: Alkermes, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Narcolepsy • Sleep Disorder

A Study to Evaluate the Efficacy, Safety and Tolerability of ALKS 2680 in Adults With Narcolepsy Type 1 (Brilliance NT1 - 304) (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Alkermes, Inc.

New P3 trial • Narcolepsy • Sleep Disorder

Brilliance NT2: A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 2 (clinicaltrials.gov) - P3 | N=176 | Not yet recruiting | Sponsor: Alkermes, Inc.

New P3 trial • Narcolepsy • Sleep Disorder

Brilliance NT1: A Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Alkermes, Inc.

New P3 trial • Narcolepsy • Sleep Disorder

Vibrance-2: A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Narcolepsy Type 2 (clinicaltrials.gov) - P2 | N=93 | Completed | Sponsor: Alkermes, Inc. | Active, not recruiting ➔ Completed

Trial completion • Narcolepsy • Sleep Disorder

Alkermes plc…announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to alixorexton for the treatment of narcolepsy type 1 (NT1), based on phase 1 and phase 2 clinical data, including positive results from Vibrance-1, a large (n=92) phase 2 study evaluating alixorexton in patients with NT1. (Yahoo Finance)

Breakthrough therapy • Narcolepsy

Vibrance-2: A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Narcolepsy Type 2 (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Alkermes, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Aug 2025 ➔ Nov 2025

Enrollment closed • Trial primary completion date • Narcolepsy • Sleep Disorder

Understanding idiopathic hypersomnia: diagnosis, pathophysiology, and management. (PubMed, Curr Opin Pulm Med) - "Growing insights into the pathophysiology and clinical features of idiopathic hypersomnia have led to improved diagnostic clarity and therapeutic innovation. These developments carry significant implications for clinical practice, offering hope for better symptom control and quality of life in affected individuals. Ongoing research is crucial for refining treatment strategies and deepening our understanding of this complex condition."

Journal • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Hypocretin: a promising target for the regulation of homeostasis. (PubMed, Front Neurosci) - "Dual hypocretin receptor antagonists (DORAs), such as suvorexant and daridorexant, are clinically approved for insomnia. Selective HCRT-2R agonists-including TAK-861 and ALKS-2680-are in clinical trials for NT1 and show encouraging results. Additionally, HCRT-2R antagonists like seltorexant are being explored for major depressive disorder. This review will highlight the anatomical distribution, receptor mechanisms, and physiological functions of the hypocretin system. It will also focus to discuss its role in narcolepsy, metabolic regulation, and mood disorders, while addressing key challenges and open questions that must be resolved to fully harness hypocretin's therapeutic potential."

Journal • Review • Cataplexy • CNS Disorders • Depression • Excessive Daytime Sleepiness • Insomnia • Major Depressive Disorder • Mood Disorders • Narcolepsy • Psychiatry • Sleep Disorder • LEP

A Phase 2, Randomized, Placebo-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of Alixorexton (ALKS 2680) in Patients With Idiopathic Hypersomnia: Study Design and Methods for Vibrance-3 (WSS 2025) - P2 | "Findings from the Vibrance-3 study will inform further clinical development of alixorexton in patients with IH. The phase 2 Vibrance-1 (NCT06358950) and Vibrance-2 (NCT06555783) studies are evaluating alixorexton in patients with narcolepsy type 1 and narcolepsy type 2, respectively."

Clinical • P2 data • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Improvement in Patient-reported Cognitive Functioning in Patients with Narcolepsy Type 1 Treated with the Orexin 2 Receptor Agonist Alixorexton (ALKS 2680) (WSS 2025) - No abstract available

Clinical • Narcolepsy • Sleep Disorder