Alkermes Presents Detailed Positive Results from Vibrance-1 Phase 2 Study of Alixorexton in Patients with Narcolepsy Type 1 at World Sleep Congress 2025

– First Orexin 2 Receptor Agonist to Demonstrate Clinically Meaningful and Statistically Significant Impact on Wakefulness, Cognition and Fatigue with Once-Daily Dosing Across a Range of Doses –

– Alixorexton Was Generally Well Tolerated at All Doses Tested –

– Company to Host Investor Webcast on Monday, Sept. 8 at 8:00 a.m. ET –

DUBLIN, Sept. 7, 2025 /PRNewswire/ -- Alkermes plc (Nasdaq: ALKS) today announced detailed positive results from the Vibrance-1 phase 2 study evaluating alixorexton in patients with narcolepsy type 1 (NT1). Alixorexton, formerly ALKS 2680, is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in phase 2 development as a once-daily treatment for NT1, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). The randomized, placebo-controlled, six-week, double-blind phase 2 study conducted in 92 patients with NT1 demonstrated clinically meaningful and statistically significant improvements in wakefulness, cognition and fatigue that were sustained over the six-week treatment period. Alixorexton was generally well tolerated at all doses tested (4 mg, 6 mg and 8 mg).

"The detailed Vibrance-1 dataset presented at World Sleep highlights the robust efficacy of once-daily alixorexton in improving wakefulness and reducing excessive daytime sleepiness in patients with narcolepsy type 1, along with its generally well tolerated safety profile. The improvements in patient-reported outcomes, especially those related to fatigue and cognitive function, suggest that alixorexton may offer meaningful relief across a spectrum of symptoms that impact patients," said Giuseppe Plazzi, M.D., Ph.D., Neurologist, Director of the Narcolepsy Center at the IRCCS of the Neurological Sciences of Bologna and Professor of Childhood Neuropsychiatry at the University of Modena and Reggio Emilia. "These data underscore alixorexton's potential to be an important new treatment option for narcolepsy type 1 and to reduce the broader disease burden of this complex neurological disorder."

The data were presented in three oral presentations at World Sleep Congress, taking place Sept. 5-10, 2025 in Singapore. Prespecified analyses are included in the table below. Key highlights include:

• Once-daily alixorexton met the primary endpoint across all doses tested, demonstrating statistically significant, clinically meaningful and dose-dependent improvements from baseline compared to placebo in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) at week six. Patients had a mean sleep latency of approximately 3 minutes at baseline. All alixorexton dose groups achieved normative wakefulness on the MWT (mean sleep latency ≥20 minutes), with observed mean sleep latency of approximately 24 minutes, 26 minutes and 28 minutes for the 4, 6 and 8 mg doses, respectively.
• Alixorexton demonstrated robust and clinically meaningful improvements on the key secondary endpoint evaluating change from baseline versus placebo on the Epworth Sleepiness Scale (ESS) at week six.1 Patients had a mean ESS score of 18.5 at baseline. Improvements in ESS were sustained in the normal range (a score of ≤10) for all doses tested across all timepoints during the six-week double-blind treatment period and the subsequent open-label extension period through week 13.2
• On the key secondary endpoint evaluating mean weekly cataplexy rates, alixorexton demonstrated numerical and clinically meaningful improvements across all doses compared to placebo at weeks five and six3 and, on the pre-specified analysis, achieved statistical significance at the 6 mg dose. More than 40% of patients at the 6 mg and 8 mg doses achieved 100% reduction in cataplexy during week six of the study.
• Vibrance-1 also included a range of exploratory patient-reported outcome measures. Alixorexton drove statistically significant and clinically meaningful improvements from baseline compared to placebo in disease severity, fatigue and cognitive impairment. At week six, most patients receiving alixorexton reported mild narcolepsy severity.4 Across all timepoints and all alixorexton dose groups, mean cognitive impairment scores fell within the lowest severity category of "none or minimal" impairment and mean fatigue scores fell into the "normal" range—effectively achieving normalization across both cognition and fatigue.5,6