FDA Grants Breakthrough Therapy Designation to Alixorexton for Narcolepsy Type 1

The US Food & Drug Administration (FDA) granted a Breakthrough Therapy Designation to alixorexton for the treatment of narcolepsy type 1, announced by Alkermes plc on January 6, 2026.1

“Alixorexton may offer substantial improvements over available therapy for people living with narcolepsy type 1, a community that has continued to face profound unmet medical needs despite available treatments,” said Craig Hopkinson, MD, chief medical officer and executive vice president of research & development at Alkermes, in a statement.1 “This Breakthrough Therapy designation underscores the strength of alixorexton’s initial clinical data and supports our conviction that targeting the orexin pathway has the potential to fundamentally shift treatment expectations for central disorders of hypersomnolence.”

The Breakthrough Therapy Designation was based on positive results from a phase 1 trial and Vibrance-1, a large randomized, placebo-controlled, 6-week, double-blind phase 2 study assessing alixorexton among 92 patients with narcolepsy type 1.2 Alixorexton, formerly referred to as ALKS 2680, is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist that is also in development for narcolepsy type 2 and idiopathic hypersomnia.1

Orexin, a neuropeptide produced in the lateral hypothalamus, plays a central role in regulating wakefulness by activating widespread arousal pathways. Targeting the orexin system may reduce excessive daytime sleepiness across hypersomnolence disorders, even when orexin deficiency is not the primary cause.

In Vibrance-1, alixorexton met the primary endpoint across all doses (4 mg, 6 mg, and 8 mg), exhibiting statistically significant and dose-dependent improvements from baseline compared to placebo in wakefulness on the Maintenance of Wakefulness Test (MWT) in patients with narcolepsy type 1.2 All dose levels met criteria for normative wakefulness on the MWT (mean sleep latency ≥ 20 minutes), with mean sleep latencies of approximately 24, 26, and 28 minutes for the 4 mg, 6 mg, and 8 mg doses, respectively. Vibrance-1 also demonstrated clinically meaningful and statistically significant improvements in cognition and fatigue over the 6-week treatment period.

“If approved, alixorexton’s differentiated profile and compelling efficacy may represent a new standard of care in narcolepsy type 1,” Hopkinson continued.1 “We look forward to working closely with the FDA as we plan to advance alixorexton into phase 3 development later this quarter.”

References

1. Alixorexton Granted Breakthrough Therapy Designation by U.S. FDA for the Treatment of Narcolepsy Type 1. BusinessWire. Published January 6, 2025. Accessed January 6, 2026. https://www.businesswire.com/news/home/20260106871102/en/Alixorexton-Granted-Breakthrough-Therapy-Designation-by-U.S.-FDA-for-the-Treatment-of-Narcolepsy-Type-1

2. Kuntz L. Alixorexton for Narcolepsy Type 1: New Detailed Positive Phase 2 Results From Vibrance-1 Study. Psychiatric Times. Published September 9, 2025. Accessed January 6, 2026. https://www.psychiatrictimes.com/view/alixorexton-for-narcolepsy-type-1-new-detailed-positive-phase-2-results-from-vibrance-1-study