ALKS 2680 · program

Alixorexton for Idiopathic Hypersomnia

Phase 2RecruitingAlkermes plc (ALKS)
  • Orphan Drug

Indications for ALKS 2680: Narcolepsy · Phase 3 Idiopathic Hypersomnia · Phase 2

Alixorexton (ALKS 2680), an oral, once-daily, selective OX2R agonist, is in Phase 2 development for idiopathic hypersomnia (IH) via the Vibrance-3 study (NCT06843590), a randomized, double-blind, parallel-group, dose-range-finding trial. Approximately 96 adults with IH (diagnosed per ICSD-3-TR) are randomized 1:1:1:1 to placebo or alixorexton 10, 14, or 18 mg once daily for 8 weeks following a 2-week washout; the primary endpoint is change in Epworth Sleepiness Scale (ESS) from baseline to Week 8 and the key secondary is change in the Idiopathic Hypersomnia Severity Scale (IHSS). The study started 22 May 2025 and is recruiting, with estimated primary completion in November 2026. The U.S. FDA granted alixorexton orphan drug designation for IH (announced 15 June 2026). IH is a non-lead indication within Alkermes' orexin franchise (narcolepsy type 1 is the lead, now in Phase 3).

Data current as of

Development timeline

Phase 2May 2025 – Dec 2026
  1. UpcomingVibrance-3 Phase 2 topline results anticipated in idiopathic hypersomnia (primary endpoint: change in Epworth Sleepiness Scale at Week 8).
  2. U.S. FDA granted orphan drug designation to alixorexton for the treatment of idiopathic hypersomnia (the European Commission separately granted orphan designation for narcolepsy).↗
  3. Vibrance-3 Phase 2 study in idiopathic hypersomnia (NCT06843590) initiated (study start 22 May 2025): a randomized, double-blind, parallel-group, dose-range-finding study of once-daily alixorexton (10, 14, 18 mg) vs placebo over 8 weeks, primary endpoint change in ESS at Week 8.

Readouts

  • 2H 2026AnticipatedTopline dataNCT06843590

    Vibrance-3 Phase 2 topline results anticipated in idiopathic hypersomnia (primary endpoint: change in Epworth Sleepiness Scale at Week 8).

Clinical trials in Idiopathic Hypersomnia

NCT06843590ALKS 2680-203Phase 2Recruitingn=126

A Phase 2, Randomized, Parallel-Group, Double-Blind, Dose-Range-Finding Study to Evaluate the Safety and Efficacy of ALKS 2680 in Subjects With Idiopathic Hypersomnia (Vibrance-3)

Started May 2025· Primary completion Nov 2026· 📍 50 sites across 8 countries (United States, Spain, Australia, France)

Formulations

FormulationRouteRegimenPharmacokinetics
Alixorexton oral tablet
Once-daily oral doses of 4 mg, 6 mg, and 8 mg evaluated in the Vibrance-1 Phase 2 study (1 mg, 3 mg, 8 mg in Phase 1b)
OralOnce daily—

Mechanism of action (compound-wide)

Alixorexton is a potent, orally bioavailable, blood-brain-barrier-permeable, highly selective orexin receptor 2 (OX2R/HCRTR2) agonist with minimal activity at OX1R. By selectively activating OX2R on wake-promoting hypothalamic and brainstem neurons, it restores deficient orexin signaling in narcolepsy, augmenting downstream monoaminergic and cholinergic wake-promoting pathways to increase wakefulness and reduce excessive daytime sleepiness.

TargetActionAffinity
OX2RprimaryHCRTR2Agonist—ⓘ

← Full ALKS 2680 compound page (identity, identifiers, all indications)

Sources

  1. A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Idiopathic Hypersomnia (Vibrance-3, ALKS 2680-203) — ClinicalTrials.gov
  2. Alixorexton Granted Breakthrough Therapy Designation by U.S. FDA for the Treatment of Narcolepsy Type 1 — Alkermes plc / Business Wire
  3. Alkermes Announces Orphan Drug Designations for Alixorexton in the U.S. and Europe — Alkermes plc / BioSpace
  4. Alkermes Presents First Clinical Data for Orexin 2 Receptor Agonist ALKS 2680 at World Sleep Congress — Alkermes plc (via PR Newswire)