Alkermes Announces Positive Topline Results From Vibrance-1 Phase 2 Study of Once-Daily Alixorexton in Patients With Narcolepsy Type 1

– Alixorexton Demonstrated Clinically Meaningful and Statistically Significant Improvements in Wakefulness at All Doses Tested Compared to Placebo in Patients With Narcolepsy Type 1 –

– Alixorexton Demonstrated Robust and Consistent Improvements in Patient-Reported Outcomes Related to Disease Severity, Fatigue and Cognition at All Doses Tested –

– Alixorexton Was Generally Well Tolerated at All Doses Tested –

– Detailed Results to Be Presented at Upcoming World Sleep Congress –

– Data Support Advancement of Alixorexton to Phase 3 Development in Narcolepsy –

DUBLIN, July 21, 2025 /PRNewswire/ -- Alkermes plc (Nasdaq: ALKS) today announced positive topline results from the randomized double-blind treatment period of the Vibrance-1 phase 2 study evaluating alixorexton in patients with narcolepsy type 1 (NT1). Alixorexton, formerly referred to as ALKS 2680, is the company's novel, investigational, oral orexin 2 receptor (OX2R) agonist in phase 2 development as a once-daily treatment for NT1, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). In Vibrance-1, 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 addition to achieving normative wakefulness across all dose groups on the MWT (mean sleep latency >20 minutes), once-daily alixorexton demonstrated robust and clinically meaningful improvements compared to placebo on patient-reported outcomes related to excessive daytime sleepiness and other key symptoms such as fatigue and cognition. Alixorexton was generally well tolerated at all doses tested. These data support rapid initiation of a global phase 3 program of alixorexton in patients with NT1.

"These compelling results demonstrated that once-daily alixorexton normalized wakefulness and excessive daytime sleepiness scores in highly symptomatic patients with narcolepsy type 1 with a generally well tolerated profile across all doses tested. In addition, the initial data from patient-reported outcome measures related to fatigue and cognition are truly exciting and highlight the breadth of benefit that alixorexton may provide across multiple facets of narcolepsy. There is a clear and pressing need for new therapies for narcolepsy type 1, as patients continue to face a range of persistent symptoms that disrupt their day-to-day lives," 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 exciting data underscore the transformative potential of orexin 2 receptor agonists for the treatment of narcolepsy type 1 and highlight the differentiated features of alixorexton."

"Data from Vibrance-1 further characterize the clinical profile of alixorexton across a range of once-daily doses in a multiweek study in patients with narcolepsy type 1. Based on the positive outcomes across multiple symptoms important to patients, we are moving forward expeditiously to initiate a global phase 3 program. We look forward to sharing detailed data from Vibrance-1 at the World Sleep meeting in September," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President, Research & Development at Alkermes. "These positive topline data represent an important stride forward for the alixorexton development program and Alkermes' broader portfolio of orexin 2 receptor agonists. Alkermes is at the forefront of development in this exciting potential therapeutic category, and these data support our hypothesis that the therapeutic potential of orexin 2 receptor agonists extends beyond improvements in wakefulness to other symptoms such as fatigue and cognition in narcolepsy."

Vibrance-1 is a global, randomized, double-blind, placebo-controlled, multiple dose phase 2 study conducted in patients with NT1 (n=92). Patients were randomized (1:1:1:1) to receive a once-daily dose of alixorexton (4 mg, 6 mg or 8 mg) or placebo for six weeks.

Primary Endpoint

• Maintenance of Wakefulness Test (MWT): Across all doses tested, alixorexton demonstrated statistically significant, clinically meaningful and dose-dependent improvements from baseline in mean sleep latency compared to placebo at week six (p