LAUSR

Obstructive sleep apnea (OSA) is a common disorder characterized by repeated intermittent airway collapse—often a hypoxic event—resulting in disrupted sleep and excessive daytime sleepiness (EDS). Positive Airway Pressure (PAP) therapy reduces hypoxic events and mitigates sleep disruption, but EDS often persists. Cognitive impairment is a burdensome symptom in many patients with EDS associated with OSA, which leads to occupational and social dysfunction and degrades quality of life. Solriamfetol (Sunosi®) is approved to improve wakefulness in adults with EDS associated with OSA, but its effect on cognitive impairment was unknown. The SHARP study evaluated whether solriamfetol improves cognitive function in patients with OSA-associated EDS and impaired cognition, and the durability of cognitive effects across the day. SHARP was a randomized, double-blind, placebo-controlled, crossover trial in 59 patients with OSA-associated EDS and concurrent cognitive impairment. All patients received solriamfetol (75mg for 3 days followed by 150mg/day) for 2 weeks, and placebo for 2 weeks, with treatment periods separated by a 1-week washout. The primary endpoint was change from baseline on the Coding subtest of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which is equivalent to the Digit Symbol Substitution Test (DSST). Secondary endpoints measured durability of effect spanning an 8-hour period and Patient Global Impression of Severity (PGI-S). The study completion rate was 96.7%. Solriamfetol treatment improved performance on the DSST-RBANS compared to placebo (6.49 vs. 4.75, p=0.009), with an effect size (Cohen’s d) of 0.36. Solriamfetol also yielded improvements at post-dose timepoints throughout the day (solriamfetol-placebo difference): 2 hours (1.91, p=0.033), 4 hours (1.38, p=0.089; NS), 6 hours (2.33, p=0.004), 8 hours (1.58, p=0.022). Scores on the PGI-S improved with solriamfetol compared to placebo (-0.90 vs -0.61, p=0.034). The most common adverse events with solriamfetol treatment (incidence ≥3%) were nausea (6.9%) and anxiety (3.4%). The adverse events profile and high completion rate suggest solriamfetol (150mg/day) was well tolerated. Moreover, solriamfetol improved cognition as measured by the DSST-RBANS, demonstrated durable effects over an 8-hour period, and reduced perceptions of symptom severity. Thus, in patients with OSA-associated EDS and impaired cognition, solriamfetol durably improved cognitive performance. Axsome Therapeutics Jazz Pharmaceuticals