Alkermes’ experimental drug alixorexton met the main goals of a mid-stage study in patients with narcolepsy type 2, though results showed weaker-than-expected effects on wakefulness, reducing its competitive standing against a rival drug candidate from Centessa. Following the announcement, Alkermes’ shares fell more than 10% on Wednesday.
Vibrance-1 Trial Results
The Phase II Vibrance-1 trial evaluated alixorexton in 93 patients diagnosed with narcolepsy type 2, a condition marked by excessive daytime sleepiness and disrupted sleep-wake regulation. The drug, designed to activate the orexin 2 receptor that helps maintain wakefulness, met both primary endpoints of the eight-week study. Alkermes reported that the treatment significantly improved mean sleep latency, the time it takes for patients to fall asleep, and reduced daytime sleepiness.
Both the 14 mg and 18 mg doses met the study’s main goals, though the data indicated greater variability later in the day. The once-daily administration of alixorexton improved patients’ ability to stay awake during an eight-hour test but showed reduced effectiveness at the six- and eight-hour marks.
Analyst Commentary and Competitive Landscape
Piper Sandler analysts described the outcome as disappointing, stating that the drug underperformed on wakefulness measures compared to Centessa’s ORX750, which showed strong early efficacy at week two in a similar patient population.
According to UBS analyst So Youn Shim, alixorexton’s improvement in wakefulness was less pronounced than in Centessa’s trials for the same condition. Shim added that a potential shift to a twice-daily dosing regimen could eliminate the drug’s advantage over other candidates such as Takeda’s oveporexton.
Future Development and Strategy
Despite the mixed data, Alkermes emphasized that the study met its overall goals. “Alkermes plans to begin Phase III studies of alixorexton as quickly as possible,” said Chief Medical Officer Craig Hopkinson. He also stated that the company would test both once-daily and split dosing regimens in late-stage development.
Piper Sandler analysts cautioned that increasing the dose in the next trial carries risks, noting that such changes have not yet been validated in prior testing. They characterized this as “somewhat of a risky strategy for Alkermes, given that it would essentially be ‘flying blind’ in the phase-3 study with doses that haven’t yet been tested in phase 2.”
Alkermes intends to launch a global Phase III program in the first quarter of 2026, targeting narcolepsy type 2. Analysts from Truist Securities viewed the Phase II results as sufficient to support advancement into late-stage testing, describing the findings as highly competitive in the NT2 treatment space.
Market and Portfolio Context
Alixorexton, an oral orexin 2 receptor agonist, is also being studied in idiopathic hypersomnia and narcolepsy type 1. At the 2025 World Sleep Congress, Alkermes presented data from the same Vibrance-1 study showing improved cognition and reduced fatigue in patients with narcolepsy type 1, outcomes that Stifel analysts called notable.
Truist analysts further pointed to Alkermes’ recent $2.1 billion acquisition of Avadel, which added the FDA-approved narcolepsy treatment Lumryz to its portfolio, as a move that could strengthen its position in the sleep disorder market. Lumryz is projected to generate between $265 million and $275 million in revenue this year.
Following the release of the trial data, U.S.-listed shares of Centessa rose more than 17% as investor confidence shifted toward the company’s competing drug candidate.
Market Reaction
Following the release of the alixorexton trial data, U.S.-listed shares of Centessa rose more than 17%, as investor confidence shifted toward Centessa’s competing drug candidate. The market’s strong reaction reflected not just the competitive risk from alixorexton, but also how sensitive investors are to late-day efficacy in wakefulness studies.
Broader Implications
The mixed Vibrance-2 data for alixorexton underscore several important themes in sleep-medicine development. First, even drugs that hit their primary endpoints may not deliver full-day efficacy, which can dampen enthusiasm. Second, tolerability remains a critical factor — especially for daytime wake-promoting agents; if a drug is safe but not sufficiently effective throughout the waking hours, patients and clinicians may favor alternatives.
