Alkermes plc announced the publication of data from its Vibrance-1 phase 2 study. The data evaluated alixorexton in adults with narcolepsy type 1 (NT1). The study results appeared in The Lancet Neurology. Alixorexton is a novel, investigational oral selective orexin 2 receptor (OX2R) agonist. Alkermes is developing the treatment for NT1, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH).
Following positive phase 2 Vibrance results, Alkermes has started the Brilliance Studies. This global phase 3 program evaluates once-daily and split-dose regimens. The program focuses on adults with NT1 and NT2.
- Alixorexton delivered statistically significant and clinically meaningful improvements in wakefulness and cataplexy.
- Across all tested doses, Alixorexton improved patient-reported outcomes linked to disease severity, fatigue, cognition and quality of life.
- Alixorexton was generally well tolerated across all tested doses.
Vibrance-1 Study Shows Meaningful Treatment Improvements
The Vibrance-1 phase 2 study included 92 adults with NT1. Researchers conducted a six-week randomized, placebo-controlled and double-blind treatment period. Participants could then enter an optional seven-week open-label extension. As previously announced, once-daily alixorexton produced statistically significant improvements. Researchers compared the results with placebo from baseline. The improvements covered objective and subjective measures of excessive daytime sleepiness. Researchers measured objective wakefulness through the Maintenance of Wakefulness Test (MWT). They assessed subjective sleepiness using the Epworth Sleepiness Scale (ESS).
All tested doses achieved mean sleep latency within the normative MWT range. The tested doses included 4 mg, 6 mg and 8 mg. Each group reached a mean sleep latency of at least 20 minutes at week six. The treatment also produced meaningful ESS results. Each dose group reached an ESS score of 10 or lower at week six. These results indicate improvements in excessive daytime sleepiness.
Moreover, the 6 mg alixorexton group achieved a significant reduction in weekly cataplexy rates. Researchers compared the results with placebo. Alixorexton also improved several exploratory patient-reported outcomes. These measures covered overall disease severity, fatigue, cognition and health-related quality of life. The treatment remained generally well tolerated across all tested doses. Most treatment-emergent adverse events (TEAEs) were mild or moderate. No serious TEAEs were reported during the study.
“The data published in The Lancet Neurology highlight the robust efficacy of once-daily doses of alixorexton in patients with narcolepsy type 1 across measures of wakefulness and excessive daytime sleepiness. Along with a generally well-tolerated profile, alixorexton demonstrated improvements across a broad range of symptoms that affect daily functioning, including cataplexy, overall disease severity, cognition and fatigue. These data are a substantial contribution to the evidence base supporting the potential of orexin 2 receptor agonists to transform the treatment of narcolepsy and the utility of a range of doses to address the individual needs of people living with NT1,” 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.
“In the Vibrance-1 study, alixorexton demonstrated substantial and clinically meaningful benefits across multiple dimensions of narcolepsy type 1,” said Craig Hopkinson, M.D. (MBChB), Chief Medical Officer and Executive Vice President, Research & Development at Alkermes. “The totality of evidence generated across the Vibrance phase 2 program in narcolepsy has reinforced our confidence in alixorexton’s potential to meaningfully impact the lives of people living with narcolepsy type 1 and type 2. These findings highlight the potential of alixorexton to address a broad range of symptoms that continue to burden patients despite currently available therapies. With the global Brilliance phase 3 program now underway in both narcolepsy type 1 and type 2, we are excited to continue advancing alixorexton in this next stage of development.”
Details of the Vibrance-1 Phase 2 Study
Vibrance-1 was a randomized, double-blind, dose-range-finding, placebo-controlled phase 2 study. The trial evaluated the safety and efficacy of alixorexton in adults with NT1. The study enrolled 92 participants. Researchers randomly assigned participants to receive 4 mg, 6 mg or 8 mg of alixorexton. Another group received placebo. Participants took their assigned treatment once daily for six weeks. The primary endpoint measured changes in wakefulness from baseline. Researchers used mean sleep latency on the Maintenance of Wakefulness Test at week six.
The study also included several secondary endpoints. These included changes in ESS scores and weekly cataplexy rates. Researchers also assessed the incidence of adverse events. In addition, the study included exploratory patient-reported outcome measures. These measures examined disease severity, fatigue and cognition. Participants who completed the double-blind period could continue into a seven-week open-label safety extension. They could then enter a long-term safety study.
Alixorexton Advances in Narcolepsy Research
Alixorexton was previously known as ALKS 2680. It is an investigational oral selective OX2R agonist. Alkermes is studying medicine for NT1, NT2 and IH. Orexin is a neuropeptide produced in the lateral hypothalamus. Researchers consider orexin a key regulator of wakefulness. It activates several downstream pathways that promote wakefulness throughout the brain.
Therefore, targeting the orexin system may help address excessive daytime sleepiness. This approach could apply across different hypersomnolence disorders. Alixorexton is currently being evaluated in the phase 3 Brilliance Studies. These studies include patients with NT1 and NT2. The company is also evaluating alixorexton in the phase 2 Vibrance-3 study for IH.
The U.S. Food and Drug Administration granted alixorexton Breakthrough Therapy designation for NT1. The FDA also granted Orphan Drug Designation for IH. Furthermore, the European Commission granted Orphan Drug Designation to alixorexton. The designation covers its development for narcolepsy. With the Brilliance phase 3 program underway, Alkermes continues advancing alixorexton. The company aims to evaluate its potential across multiple narcolepsy patient populations.
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News Source: Businesswire.com
