New data from a long-term extension study demonstrates sustained improvements in wakefulness, cognition, and fatigue for adults with narcolepsy type 1 and type 2.
Key takeaways:
- Alixorexton showed sustained, clinically meaningful improvements on the Maintenance of Wakefulness Test and Epworth Sleepiness Scale at week 24.
- Patient-reported outcomes indicated maintained improvements in cognition and fatigue across all dose groups compared to baseline.
- The investigational orexin 2 receptor agonist was generally safe and well-tolerated, with no serious treatment-emergent adverse events reported.
Alkermes plc recently shared results from a planned interim analysis of an ongoing long-term extension study evaluating alixorexton in adults with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2).
Across all dose groups in both NT1 and NT2 participants, alixorexton demonstrated sustained clinically meaningful improvement from baseline on the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) at week 24. This represents approximately nine months after the first dose for participants treated with alixorexton in the randomized double-blind period of the phase 2 studies.
Alixorexton also demonstrated sustained and clinically meaningful improvement from baseline across patient-reported outcomes evaluating cognition and fatigue at week 24. The novel, investigational, oral, selective orexin 2 receptor agonist was generally safe and well-tolerated at all doses tested.
“For people living with narcolepsy, symptom burden extends beyond excessive daytime sleepiness and can affect cognitive function and fatigue. It is exciting to see clinically meaningful improvements sustained across these important measures in this analysis of the long-term extension study of alixorexton in patients with narcolepsy type 1 and type 2. The consistency of the data in up to nine months of treatment provides further evidence that alixorexton, across a range of doses, has the potential to address important aspects of disease burden of narcolepsy regardless of narcolepsy type 1 or type 2 diagnosis,” says Yves Dauvilliers, MD, PhD, professor of neurology and physiology, and director of the sleep-wake disorders center at the University of Montpellier, France, and coordinator of the French National Reference Center for Rare Diseases dedicated to narcolepsy and hypersomnias, in a release.
This ongoing open-label extension study is designed to evaluate the long-term safety, tolerability, and durability of treatment effect of alixorexton. The interim analysis reflects safety and tolerability data as of the May 12, 2026, data cutoff and efficacy measures collected at week 24.
Narcolepsy Type 1 Findings
In the phase 2 parent study, alixorexton demonstrated clinically meaningful improvements in wakefulness and cataplexy in participants with NT1 randomized to receive a once-daily dose of alixorexton (4 mg, 6 mg, or 8 mg) or placebo. Approximately 85% of participants enrolled in the long-term extension, and as of the data cutoff, approximately 90% of these participants remained on treatment.
Endpoints evaluating durability of effect in NT1 participants include:
- All alixorexton dose groups for NT1 achieved normative wakefulness on the MWT (mean sleep latency ≥20 minutes) at week 24 of the long-term extension, with a mean observed mean sleep latency of approximately 29 minutes across LTE participants.
- Improvements in ESS from baseline were sustained in the normal range (a score of ≤10) for all doses tested throughout the LTE, with a mean observed ESS of 7.5 at week 24 across long-term extension participants.
- Alixorexton demonstrated improvements from baseline on weekly cataplexy rate at all long-term extensionassessment timepoints. At week 24, the median weekly cataplexy rate across long-term extension participants was 2.
Improvements from baseline in exploratory patient-reported outcomes evaluating cognition and fatigue were generally maintained across dose groups. At week 24, most NT1 participants across all doses had cognitive functioning scores within the normal range, and mean fatigue scores were within the normal range across all doses. Prior to treatment with alixorexton in the parent study, participants reported mean scores of moderate cognitive impairment and fatigue.
Alixorexton was generally safe and well-tolerated across all doses tested in the long-term extension. No serious treatment-emergent adverse events were reported. The most common were headache, micturition urgency, pollakiuria, and nasopharyngitis.
Narcolepsy Type 2 Findings
In the phase 2 parent study, alixorexton demonstrated improvements in wakefulness in participants with NT2 randomized to receive a once-daily dose of alixorexton (10 mg, 14 mg, or 18 mg) or placebo. Approximately 70% enrolled in the long-term extension, and as of the data cutoff, approximately 80% remained on treatment.
Endpoints evaluating durability of effect in NT2 participants include:
- All alixorexton dose groups for NT2 demonstrated further improvement on the MWT at week 24 of the long-term extension, with a mean observed mean sleep latency of approximately 18 minutes across LTE participants.
- Improvements in ESS were sustained in the normal range (a score of ≤10) for the 14 mg and 18 mg dose groups throughout the long-term extension. The mean observed ESS was 8.9 at week 24.
Improvements from baseline in exploratory outcomes evaluating cognition and fatigue were generally maintained in NT2 participants across dose groups. At week 24, most NT2 participants across all doses had cognitive functioning scores within the normal or mild range, and mean fatigue scores were within the normal range. Before treatment, participants reported overall mean scores of moderate cognitive impairment and fatigue.
Safety profiles in NT2 participants were consistent, with no serious treatment-emergent adverse events reported. The most common were insomnia, headache, pollakiuria, and upper respiratory tract infection.
“These long-term results represent a significant contribution to our understanding of alixorexton as a potential new treatment option for patients with narcolepsy. We are particularly encouraged by the durability of effect observed across multiple dimensions of the disease, including wakefulness, cognition, and fatigue, together with a safety profile that continued to be generally well tolerated. These data also underscore the importance of dosing flexibility to meet individual needs across narcolepsy patients with known orexin deficiency as well as patients with normal orexin tone,” says Craig Hopkinson, MD, chief medical officer and executive vice president, research & development at Alkermes, in a release.
Alixorexton is currently being evaluated in the phase 3 Brilliance studies in adults with NT1 and NT2, and in the phase 2 Vibrance-3 study in adults with idiopathic hypersomnia.
