Centessa's ORX750 Gains Momentum as Alkermes' Narcolepsy Trial Results Encourage.

Alkermes reported top-line data for its Phase 2 Vibrance-1 trial of alixorexton in narcolepsy type 1. Leerink views the results as "encouraging" for Centessa's ORX750, validating the orexin agonist class and suggesting room for differentiation on efficacy and/or safety. Leerink maintains an Outperform rating on Centessa shares.

Alkermes plc (Nasdaq: ALKS) has announced positive topline results from the Vibrance-1 phase 2 study evaluating alixorexton in patients with narcolepsy type 1 (NT1). The study demonstrated statistically significant, clinically meaningful, and dose-dependent improvements in wakefulness across all doses tested compared to placebo. The results were presented in a press release dated July 21, 2025 [1].

Alixorexton, an investigational, oral orexin 2 receptor (OX2R) agonist, achieved the primary endpoint of the study, which was to improve wakefulness as measured by the Maintenance of Wakefulness Test (MWT). The drug showed robust and consistent improvements in patient-reported outcomes related to excessive daytime sleepiness, fatigue, and cognition. It was generally well-tolerated across all doses tested [1].

The study enrolled 92 patients with NT1, who were randomized to receive alixorexton at doses of 4 mg, 6 mg, or 8 mg, or placebo once-daily for six weeks. The primary endpoint was met across all doses, with statistically significant improvements in mean sleep latency (p0.0001 at all doses). Secondary endpoints, including the Epworth Sleepiness Scale (ESS) and weekly cataplexy rates, also showed significant improvements [1].

Leerink Research views these results as encouraging for Centessa's ORX750, validating the orexin agonist class and suggesting potential for differentiation in efficacy and safety. Leerink maintains an Outperform rating on Centessa shares [2].

Alkermes plans to present detailed data from the Vibrance-1 study at the upcoming World Sleep Congress in September. The company is also advancing alixorexton to phase 3 development in NT1, with ongoing phase 2 studies for narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) [1].

References:
[1] Alkermes plc. (2025). Alkermes Announces Positive Topline Results from Vibrance-1 Phase 2 Study Evaluating Alixorexton in Patients with Narcolepsy Type 1. [URL](https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-positive-topline-results-vibrance-1-phase-2)
[2] Leerink Research. (2025). Alkermes' Positive Vibrance-1 Data Encouraging for Centessa's ORX750. [URL](https://www.leerink.com/research/alkermes-positive-vibrance-1-data-encouraging-for-centessas-orx750)