ALKS 2680 · program

Alixorexton for Narcolepsy

Phase 3ActiveAlkermes plc (ALKS)
  • Breakthrough Therapy
  • Orphan Drug

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

Alixorexton (ALKS 2680) is in Phase 3 development for narcolepsy type 1 (lead indication). Following positive Phase 2 results from the Vibrance-1 study in NT1 (NCT06358950; all doses met the primary MWT endpoint), the FDA granted Breakthrough Therapy designation for NT1 on 2026-01-06. Alkermes initiated the global Phase 3 Brilliance program (three 12-week studies across NT1 and NT2) on 2026-04-06. The positive Vibrance-2 Phase 2 study in NT2 (NCT06555783) supports the NT2 Phase 3 study, and Vibrance-3 in idiopathic hypersomnia (NCT06843590) is ongoing in Phase 2. Alixorexton also holds U.S. orphan drug designation for idiopathic hypersomnia and EU orphan drug designation for narcolepsy.

Data current as of

Development timeline

Phase 3Apr 2026 – May 2027
  1. UpcomingPhase 3 Brilliance NT1 (Study 302) topline anticipated, evaluating the primary MWT endpoint at Week 12 in narcolepsy type 1.
  2. UpcomingVibrance-3 Phase 2 topline results anticipated in idiopathic hypersomnia (primary endpoint ESS at Week 8).
  3. Alkermes initiated the Phase 3 Brilliance program evaluating alixorexton in narcolepsy type 1 and type 2: three 12-week, randomized, double-blind, placebo-controlled studies (Brilliance NT1 Study 302 NCT07455383 and Study 304 NCT07540897; Brilliance NT2 Study 303 NCT07502443).↗
Phase 2Jul 2025 – Jan 2026
  1. FDA granted Breakthrough Therapy designation to alixorexton for the treatment of narcolepsy type 1, based on Phase 1 and Phase 2 data including the positive Vibrance-1 study.↗
  2. metVibrance-2 Phase 2 study in narcolepsy type 2 met the primary MWT endpoint at 14 mg and 18 mg, with ESS significant at 18 mg (p<0.05 adjusted).↗
  3. metVibrance-1 Phase 2 study in narcolepsy type 1 met the primary MWT endpoint across all doses (4, 6, 8 mg) with statistically significant, dose-dependent improvements in wakefulness vs placebo.↗

Readouts

  • May 2027AnticipatedTopline dataNCT07455383

    Phase 3 Brilliance NT1 (Study 302) topline anticipated, evaluating the primary MWT endpoint at Week 12 in narcolepsy type 1.

  • 2H 2026AnticipatedTopline dataNCT06843590

    Vibrance-3 Phase 2 topline results anticipated in idiopathic hypersomnia (primary endpoint ESS at Week 8).

  • 2025-11-12ReportedTopline datametNCT06555783

    Vibrance-2 Phase 2 study in narcolepsy type 2 met the primary MWT endpoint at 14 mg and 18 mg, with ESS significant at 18 mg (p<0.05 adjusted). ↗

  • 2025-07-09ReportedTopline datametNCT06358950

    Vibrance-1 Phase 2 study in narcolepsy type 1 met the primary MWT endpoint across all doses (4, 6, 8 mg) with statistically significant, dose-dependent improvements in wakefulness vs placebo. ↗

Clinical trials in Narcolepsy

NCT07455383ALKS 2680-302Phase 3Recruitingn=150

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1 (Brilliance NT1 - 302)

Started Apr 2026· Primary completion May 2027· 📍 17 sites across 2 countries (United States, Canada)

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)

NCT06555783ALKS 2680-202Phase 2Completedn=93

A Phase 2, Parallel-Group, Dose-Range-Finding Study With Randomized Double-Blind Treatment and Open-Label Periods to Evaluate the Safety and Efficacy of ALKS 2680 in Subjects With Narcolepsy Type 2 (Vibrance-2)

Started Jul 2024· Primary completion Nov 2025· 📍 47 sites across 8 countries (United States, Italy, Spain, Belgium)

metsecondaryChange in Epworth Sleepiness Scale (ESS) from baseline to Week 8 — Clinically meaningful reductions in excessive daytime sleepiness across all doses; statistical significance reached at 18 mg. (18 mg P<0.05 (adjusted for multiplicity))

ESS achieved statistical significance at the 18 mg dose (p<0.05 adjusted), with clinically meaningful improvements in daytime sleepiness across all doses vs placebo.

metprimaryChange in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) from baseline to Week 8 — Clinically meaningful improvements in MSL vs placebo across all doses (10, 14, 18 mg); statistical significance reached at 14 mg and 18 mg. (14 mg and 18 mg P<0.05 (adjusted for multiplicity))

Met the primary MWT endpoint at the 14 mg and 18 mg doses (p<0.05 adjusted), with clinically meaningful improvements in wakefulness across all doses vs placebo over 8 weeks.

NCT06358950ALKS 2680-201Phase 2Completedn=92

A Phase 2, Parallel-Group, Dose-Range-Finding Study With Randomized Double-Blind Treatment and Open-Label Periods to Evaluate the Safety and Efficacy of ALKS 2680 in Subjects With Narcolepsy Type 1 (Vibrance-1)

Started Mar 2024· Primary completion Jun 2025

metprimaryChange in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) from baseline to Week 6 — LSM difference from placebo: 4 mg +22.2 min; 6 mg +24.1 min; 8 mg +26.0 min. All active dose groups reached normative wakefulness (observed MSL ~24, 26, and 28 min vs ~3 min at baseline). (4 mg P=0.01; 6 mg P<0.0001; 8 mg P<0.0001)

Met the primary endpoint across all doses with statistically significant, clinically meaningful, dose-dependent improvements in wakefulness on MWT vs placebo, sustained over 6 weeks.

metsecondaryChange in Epworth Sleepiness Scale (ESS) at Week 6 — LSM difference from placebo: 4 mg -6.4; 6 mg -8.7; 8 mg -8.3 (4 mg P=0.01; 6 mg P<0.0001; 8 mg P<0.0001)

Clinically meaningful reductions in excessive daytime sleepiness on the ESS across all doses vs placebo at Week 6.

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 Efficacy and Safety of ALKS 2680 in Adults With Narcolepsy Type 1 (Brilliance NT1 - 302) — ClinicalTrials.gov
  2. A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Idiopathic Hypersomnia (Vibrance-3, ALKS 2680-203) — ClinicalTrials.gov
  3. A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Narcolepsy Type 1 (Vibrance-1, ALKS 2680-201) — ClinicalTrials.gov
  4. A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Narcolepsy Type 2 (Vibrance-2, ALKS 2680-202) — ClinicalTrials.gov
  5. Alixorexton for Narcolepsy Type 1: New Detailed Positive Phase 2 Results From Vibrance-1 Study — Psychiatric Times
  6. Alixorexton Granted Breakthrough Therapy Designation by U.S. FDA for the Treatment of Narcolepsy Type 1 — Alkermes plc / Business Wire
  7. Alkermes Announces Initiation of Phase 3 Brilliance Studies Evaluating Alixorexton for the Treatment of Narcolepsy Type 1 and Type 2 — Alkermes plc
  8. Alkermes Announces Positive Topline Results From Vibrance-1 Phase 2 Study of Once-Daily Alixorexton in Patients With Narcolepsy Type 1 — Alkermes plc
  9. Alkermes Announces Positive Topline Results From Vibrance-2 Phase 2 Study of Once-Daily Alixorexton in Patients With Narcolepsy Type 2 — Alkermes plc / PR Newswire
  10. Alkermes Presents First Clinical Data for Orexin 2 Receptor Agonist ALKS 2680 at World Sleep Congress — Alkermes plc (via PR Newswire)