1023 Solriamfetol and Maintenance of Wakefulness Outcomes in Patients with Narcolepsy and Obstructive Sleep Apnea

Abstract Introduction Patients with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) struggle to maintain wakefulness. Solriamfetol (Sunosi®) is a dopamine/norepinephrine reuptake inhibitor with agonistic properties at TAAR1 and serotonin 1A receptors; it is approved to treat EDS associated with narcolepsy (75–150 mg/day) or OSA (37.5–150 mg/day). This post-hoc analysis characterized the effects of solriamfetol on the propensity of participants with EDS associated with narcolepsy or OSA to maintain wakefulness. Methods The safety and efficacy of solriamfetol has been evaluated in participants with EDS and narcolepsy or OSA in the phase 3 trials, TONES 2 and TONES 3. Participants were randomized to placebo or solriamfetol (37.5 mg OSA only, 75 mg, 150 mg, or 300 mg) once daily for 12 weeks. This post-hoc analysis evaluated the proportion of participants who achieved improvement from baseline on various 40-minute Maintenance of Wakefulness Test (MWT) thresholds (≥5, ≥10, ≥15, and ≥20 minutes) and mean sleep latencies ≥30 and ≥40 minutes at weeks 1, 4, and 12. Comparisons between solriamfetol and placebo were evaluated using Fisher’s exact test. Results A greater proportion of participants with narcolepsy achieved improvement from baseline of ≥15 and ≥20 minutes on the MWT with solriamfetol 150 mg (36% and 18%, respectively) and 300 mg (38% and 28%) compared with placebo (4% and 4%) at week 12 (P≤0.028); findings were similar at week 12 in participants with OSA with solriamfetol 75 mg (28% and 13%), 150 mg (37% and 25%), and 300 mg (44% and 28%) compared with placebo (8% and 3%; P≤0.034). A greater proportion of participants with narcolepsy achieved MWT sleep latency ≥30 minutes at week 12 with solriamfetol 150 mg (24%) and 300 mg (30%) compared with placebo (2%; P≤0.002); results were similar in participants with OSA for MWT sleep latency ≥30 minutes at week 12 with solriamfetol 75 mg (28%), 150 mg (34%), and 300 mg (44%) compared with placebo (11%; P≤0.012). Conclusion These findings suggest solriamfetol leads to substantial improvements on objective propensity to stay awake in a large proportion of patients with narcolepsy or OSA when compared with placebo. Support (if any) Axsome Therapeutics, Jazz Pharmaceuticals