FDA Grants Breakthrough Therapy Designation to Alixorexton for the Treatment of Narcolepsy Type 1

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Alkermes’ alixorexton for the treatment of narcolepsy type 1 (NT1). 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).¹

This designation is based on phase 1 and phase 2 clinical data, including positive results from Vibrance-1, a large phase 2 study evaluating alixorexton in 92 participants with NT1.

“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. 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. If approved, alixorexton’s differentiated profile and compelling efficacy may represent a new standard of care in narcolepsy type 1. We look forward to working closely with the FDA as we plan to advance alixorexton into phase 3 development later this quarter,” said Craig Hopkinson, MD, the chief medical officer and executive vice president of research & development at Alkermes.

In the Vibrance-1 phase 2 study, alixorexton met the primary endpoint across all doses tested, demonstrating statistically significant, clinically meaningful and dose-dependent improvements from baseline compared to placebo in wakefulness on the Maintenance of Wakefulness Test (MWT) in patients with NT1. Alixorexton was generally well tolerated at all doses tested.

In Vibrance-2, 93 participants with NT2 were randomly assigned (1:1:1:1) to receive a once-daily dose of alixorexton (10 mg, 14 mg, or 18 mg) or placebo for 8 weeks. Once-daily alixorexton met the dual primary endpoints, demonstrating statistically significant and clinically meaningful improvements from baseline compared with placebo on the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) at week 8.^2,3

On the MWT, alixorexton demonstrated clinically meaningful improvements from baseline in mean sleep latency compared to placebo at week 8 at all doses tested. Based on the prespecified analysis, the 14 mg and 18 mg doses achieved statistical significance (P<0.05 adjusted for multiplicity).²

On the ESS, alixorexton demonstrated clinically meaningful improvements from baseline in excessive daytime sleepiness compared with placebo at week 8 at all doses tested. Based on the prespecified analysis, the 18 mg dose achieved statistical significance (P<0.05 adjusted for multiplicity).²

Alkermes plans to initiate the alixorexton narcolepsy global phase 3 program in the first quarter of 2026.

References

1. Alixorexton granted breakthrough therapy designation by U.S. FDA for the treatment of narcolepsy type 1. News release. January 6, 2026. Accessed January 7, 2026. https://investor.alkermes.com/news-releases/news-release-details/alixorexton-granted-breakthrough-therapy-designation-us-fda

2. Alkermes announces positive topline results from Vibrance-2 phase 2 study of once-daily alixorexton in patients with narcolepsy type 2. News release. November 12, 2025. Accessed January 7, 2026. https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-positive-topline-results-vibrance-2-phase-2

3. Kuntz L. Alixorexton for treatment of narcolepsy type 2: new positive phase 2 data. Psychiatric Times. November 13, 2025. https://www.psychiatrictimes.com/view/alixorexton-for-treatment-of-narcolepsy-type-2-new-positive-phase-2-data