ATS 2026
Once-nightly pill improves obstructive sleep apnea in phase 3 trial
Clinical Takeaway: AD109 significantly reduced apnea-hypopnea index and improved oxygenation over 26 weeks in adults with mild to severe obstructive sleep apnea who couldn't tolerate or declined PAP therapy. The investigational oral therapy may become a non-device treatment option if approved, but adverse effects led to discontinuation in about 1 in 5 patients.
Continuous positive airway pressure (CPAP) remains the standard treatment for obstructive sleep apnea (OSA), yet many patients are unable to tolerate it or remain untreated. New phase 3 data suggest an oral therapy targeting the neuromuscular mechanisms of airway collapse may offer an alternative approach.
AD109 combines aroxybutynin and atomoxetine, two agents designed to improve upper-airway muscle tone during sleep and reduce airway collapse. In the SynAIRgy trial, 646 adults with mild to severe OSA across 69 sites in the United States and Canada were randomized to AD109 or placebo if they couldn't tolerate or had refused PAP therapy. The study population had a median age of 58 years, median BMI of 32.4 kg/m², and was nearly evenly split by sex.
At 26 weeks, AD109 reduced apnea-hypopnea index by a mean of 4.0 events/hour more than placebo. This corresponded to a model-estimated 44.1% reduction from baseline with AD109 vs. 17.6% with placebo. The drug also improved oxygen desaturation index and hypoxic burden, and benefits were seen as early as week 4.
More than 40% of treated patients improved by at least one OSA severity category, and 17.6% achieved complete disease control, defined as apnea-hypopnea index below 5 events/hour. Improvements were seen across sex, BMI class, and baseline OSA severity.
The study’s primary symptom outcome didn't clearly separate from placebo in the main intent-to-treat analysis. PROMIS-Fatigue improved in both groups, but the between-group difference didn't meet statistical significance. PROMIS-Sleep Impairment also wasn't significantly different between groups.
Adverse effects were common and led to treatment discontinuation in 21.2% of patients receiving AD109 vs. 3.1% receiving placebo. The most common adverse effects were dry mouth, insomnia, nausea, and urinary hesitation. No serious treatment-related adverse events were reported.
“In many other chronic diseases, such as cardiovascular disease, asthma, or type 2 diabetes, it would be unthinkable for the majority of diagnosed patients to remain untreated or undertreated. Yet that remains the reality in OSA,” said Patrick John Strollo, MD, of the University of Pittsburgh Medical Center. “An oral pill that targets the underlying neuromuscular drivers of airway collapse during sleep could help address this gap and broaden the range of effective options for patients who remain untreated today.”
Source: Strollo PJ, et al. (2026, May 18). American Journal of Respiratory and Critical Care Medicine. Aroxybutynin and Atomoxetine (AD109) for Obstructive Sleep Apnea: A Randomized Phase 3 Trial