In a study of 59 individuals with obstructive sleep apnea, solriamfetol yielded cognitive improvements at post-dose time points throughout the day, along with improvements in Patient Global Impression of Severity.
Data from the randomized, double-blind, placebo-controlled SHARP trial (NCT04789174) showed that treatment with solriamfetol (Sunosi; Axsome Therapeutics) was not only safe and well tolerated among individuals with obstructive sleep apnea (OSA), but provided additional benefits on cognition.1
Led by senior investigator Herriot Tabuteau, MD, the chief executive officer of Axsome, patients received solriamfetol 75 mg for 3 days followed by 150 mg/day for 2 weeks, and placebo for 2 weeks, with treatment periods separated by a 1-week washout. At the conclusion of the analysis, solriamfetol-treated individuals showed improved performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) relative to placebo (6.49 vs 4.75; P = .0009), with an effect size (Cohen’s d) of 0.36.
Presented at the 2023 SLEEP Annual Meeting, held June 3-7, in Indianapolis, Indiana, 59 patients with OSA-related excessive daytime sleepiness (EDS) and concurrent cognitive impairment were included in the trial. Patients were between the ages of 18 and 65 years old and had at least 6 hours of usual nightly total sleep time. In addition, patients either had consistent number of hours of primary positive airway pressure (PAP) therapy use for at least 5 nights/week for at least 1 month prior, had no current use of PAP therapy but a history of at least 1 month of attempting to use PAP, or a history of surgical intervention intended to treat OSA symptoms.
Change in RBANS, a measure equivalent to the Digit Symbol Substitution Test (DSST), was used as the primary outcome of the trial, with secondary end points that assessed durability of effect and Patient Global Impression of Severity (PGI-S). In total, 96.7% of the cohort completed the study, with effects on cognition seen at post-dose timepoints throughout the day. Specifically, the between group difference at 2, 4, 6, and 8 hours post-dose was 1.91 (P = .033), 1.38 (P = .089), 2.33 (P = .004), and 1.58 (P = .022), respectively.
In addition to cognitive benefits, patients on the study drug showed greater improvements on PGI-S than placebo (–0.90 vs –0.61; P = .034). Similar to previous studies, the drug maintained its safety profile, with common adverse events that included nausea (6.9%) and anxiety (3.4%).
Solriamfetol was originally approved for the treatment of EDS in adults with narcolepsy or OSA in 2019, with data from the TONES clinical program supporting its approval. Since then, it has been studied in several different trials, including SHARP and SURWEY, a study assessing real-world physician strategies. Earlier this year, data from SURWEY was published, with results showing improvements in Epworth Sleepiness Scale (ESS) scores, and typical titration of the drug at 75 mg/day.
The study, which featured retrospective chart reviews from 83 patients with EDS from Germany, revealed that almost half (43%) of patients had their treatment titrated, with 90% completing titration as prescribed. The most common starting doses overall were 75 mg/day (69%) or 150 mg/day (20%), with most of the remaining patients initiated at 37.5 mg. Patients were classified as either changeover (n = 43; 61%), add-on (n = 19; 27%), or new-to-therapy (n = 8; 11%) subgroups, based on existing EDS treatment.
From initiation to follow-up, there the mean ESS score improved from 17.6 to 13.6. ESS scores improved regardless of initiation strategy, with mean decreases of 4.1 (SD, 2.9), 3.7 (SD, 2.6), and 6.1 (SD, 3.0) points from solriamfetol initiation to follow-up in the changeover, add-on, and new-to-therapy subgroups, respectively. Overall, 91% of patients reported slight or strong improvements in their EDS after initiating solriamfetol, with results similar across subgroups. From physician perspective, most patients (94%) had slight or strong improvements in EDS.