Abstract Introduction Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness, cataplexy, and a host of other symptoms that may impair aspects of patients’ quality of life (QoL), including relationship strain, problems completing daily activities, and physical limitations. In Vibrance-1, once-daily alixorexton (ALKS 2680), a potent, oral, selective orexin 2 receptor agonist, demonstrated clinically meaningful and statistically significant improvements from baseline in wakefulness versus placebo in patients with NT1. This presentation reports improvements in QoL with alixorexton over 6 weeks of treatment in patients with NT1. Methods Vibrance-1 was a placebo-controlled, dose-ranging phase 2 study with a 6-week randomized, double-blind, parallel group treatment period followed by an optional 7-week open-label extension. After 2-week washout from narcolepsy medications, adult patients with NT1 were randomized to receive placebo or alixorexton once daily at doses of 4, 6, or 8mg. Exploratory endpoints that evaluated patients’ self-reported QoL included the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), which measures 5 domains of QoL: general productivity, activity level, vigilance, social relationships, and intimate relationships. Additional exploratory endpoints that measure health-related QoL included EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) and EuroQol Visual Analogue Scale (EQ-VAS). Statistical analyses of these endpoints were not controlled for multiplicity, so p-values are considered nominal. Results Ninety-two patients were randomized. In all alixorexton groups, overall FOSQ-10 scores significantly improved from baseline to Week (Wk) 6 (p 0.003 versus placebo). Improvements from baseline to Wk6 were observed across all 5 FOSQ-10 subdomains in all alixorexton groups and were significant at the 6 and 8mg dose groups (p≤0.005 versus placebo). In all alixorexton groups, improvements from baseline to Wk6 were observed for EQ-5D-5L scores (p=0.068, 0.002, and 0.002 for 4, 6, and 8mg versus placebo, respectively). In all alixorexton groups, mean EQ-VAS scores significantly improved from baseline to Wk6 (p 0.02 versus placebo). Conclusion In the Vibrance-1 study, alixorexton resulted in greater improvements from baseline in QoL compared with placebo across all doses at Wk6 in patients with NT1, as measured by FOSQ-10, EQ-5D-5L, and EQ-VAS. Improvements with alixorexton were observed across various subdomains of these QoL measurements, including productivity, social relationships, and perceptions of health. Support (if any) Alkermes, Inc.
Lammers et al. (Fri,) studied this question.