お知らせ • Jul 14
Alkermes Announces Interim Results From Long-Term Extension Study Of Alixorexton In Adults With Narcolepsy Type 1 And Type 2
Alkermes plc announced results from a planned interim analysis of the ongoing long-term extension (LTE) 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 of the LTE, approximately nine months after the first dose for participants treated with alixorexton in the randomized double-blind period of the Vibrance-1 and Vibrance-2 phase 2 studies. Alixorexton also demonstrated sustained and clinically meaningful improvement from baseline across patient-reported outcomes (PROs) evaluating cognition and fatigue at week 24. Alixorexton was generally safe and well tolerated at all doses tested. Alixorexton is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of NT1, NT2 and idiopathic hypersomnia (IH). This ongoing open-label extension study is designed to evaluate the long-term safety, tolerability and durability of treatment effect of alixorexton. This interim analysis reflects safety and tolerability data as of the May 12, 2026 data cutoff and efficacy measures collected at week 24 of the LTE for participants who enrolled in the LTE after completing Vibrance-1 (NT1) or Vibrance-2 (NT2), reflecting treatment with alixorexton for up to nine months. The LTE remains ongoing and is open for enrollment for participants who complete ongoing phase 2 and phase 3 studies of alixorexton. In the Vibrance-1 phase 2 parent study, alixorexton demonstrated statistically significant and clinically meaningful improvements in wakefulness and cataplexy in participants with NT1 (n=92) randomized to receive a once-daily dose of alixorexton (4 mg, 6 mg or 8 mg) or placebo. Approximately 85% of Vibrance-1 participants (n=78) enrolled in the LTE. Dose adjustment was allowed during the first four weeks of the LTE, with most participants receiving 6 or 8 mg as their most frequent dose. As of the data cutoff, approximately 90% (n=70) of these participants remained on treatment. All alixorexton dose groups for NT1 achieved normative wakefulness on the MWT (mean sleep latency (MSL) =20 minutes) at week 24 of the LTE, with a mean observed MSL 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 LTE participants. Alixorexton demonstrated improvements from baseline on weekly cataplexy rate (WCR) at all LTE assessment timepoints. At week 24, the median WCR across LTE participants was 2. Improvements from baseline in exploratory PROs evaluating cognition and fatigue were generally maintained across dose groups in the LTE. At week 24, most NT1 participants across all doses had cognitive functioning scores within the normal range, as measured by the British Columbia – Cognitive Complaints Inventory (BC-CCI), and mean fatigue scores were within the normal range, as measured by PROMIS-Fatigue, 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 LTE. No serious treatment-emergent adverse events (TEAEs) were reported. Most TEAEs were mild to moderate in severity. The most common TEAEs in the LTE were headache, micturition urgency, pollakiuria, and nasopharyngitis. In the Vibrance-2 phase 2 parent study, alixorexton demonstrated statistically significant and clinically meaningful improvements in wakefulness in participants with NT2 (n=93) randomized to receive a once-daily dose of alixorexton (10 mg, 14 mg or 18 mg) or placebo. Approximately 70% of Vibrance-2 participants (n=63) enrolled in the LTE. Dose adjustment was allowed during the first four weeks of the LTE, with most participants receiving 14 or 18 mg as their most frequent dose. As of the data cutoff, approximately 80% (n=51) of these participants remained on treatment. All alixorexton dose groups for NT2 demonstrated further improvement on the MWT at week 24 of the LTE, with mean observed MSL 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 LTE. Across LTE participants, the mean observed ESS was 8.9 at week 24. Improvements from baseline in exploratory PROs evaluating cognition and fatigue were generally maintained in NT2 participants across dose groups in the LTE. At week 24, most NT2 participants across all doses had cognitive functioning scores within the normal or mild range, as measured by the BC-CCI, and mean fatigue scores were within the normal range, as measured by PROMIS-Fatigue, across all doses. Prior to treatment with alixorexton in the parent study, participants reported overall mean scores of moderate cognitive impairment and fatigue. Alixorexton was generally safe and well tolerated across all doses tested in the LTE. No serious TEAEs were reported. Most TEAEs were mild to moderate in severity. The most common TEAEs in the LTE were insomnia, headache, pollakiuria, and upper respiratory tract infection. 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 IH (Brilliance NT1 – Study 302: NCT07455383; Brilliance NT2 – Study 303: NCT07502443; Brilliance NT1 – Study 304: NCT07540897; Vibrance-3: NCT06843590). Alixorexton (formerly referred to as ALKS 2680) is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). Orexin, a neuropeptide produced in the lateral hypothalamus, is considered to be the master regulator of wakefulness due to its activation of multiple, downstream wake-promoting pathways that project widely throughout the brain. Targeting the orexin system may address excessive daytime sleepiness across hypersomnolence disorders, whether or not deficient orexin signaling is the underlying cause of disease. Alixorexton is currently being evaluated in the phase 3 Brilliance Studies in patients with NT1 and NT2, and in the phase 2 Vibrance-3 study in patients with IH. The U.S. Food and Drug Administration (FDA) has granted alixorexton Breakthrough Therapy designation for the treatment of NT1 and Orphan Drug Designation (ODD) for the treatment of IH. The European Commission has granted ODD to alixorexton for the treatment of narcolepsy.
