Once-Nightly Oral Treatment Improved Obstructive Sleep Apnea Outcomes in Phase 3 Study

Why This Matters in Sleep Neurology

Treatment with investigational AD109 (aroxybutynin 2.5 mg/atomoxetine 75 mg; Apnimed, Cambridge, MA) was shown to reduce airway obstruction and improve oxygenation in adults with obstructive sleep apnea (OSA), according to phase 3 data presented at the 2026 American Thoracic Society International Conference and published in the American Journal of Respiratory and Critical Care Medicine. OSA is associated with sleep fragmentation, intermittent hypoxia, and neurocognitive consequences, making effective alternatives to positive airway pressure (PAP) therapy relevant for neurologists who manage sleep-related disorders and cognitive symptoms.

AD109 is a once-nightly oral combination therapy designed to address neuromuscular contributors to upper airway collapse during sleep.

Inside the SynAIRgy Data

SynAIRgy (NCT05813275) was a randomized, double-blind, placebo-controlled, 26-week trial conducted at 69 sites in the United States and Canada. The study randomized 646 adults with mild to severe OSA who were unable or unwilling to use PAP therapy; the intent-to-treat efficacy analysis included 615 participants. Median baseline apnea-hypopnea index (AHI) was 19.6 events/hour, with 35% of participants having mild OSA, 42% moderate OSA, and 23% severe OSA.

Key Findings

• AHI improved by a least-squares mean of −3.3 events/hour with AD109 vs +0.7 events/hour with placebo at week 26, for a treatment difference of −4.0 events/hour (95% CI, −6.4 to −1.6; P=.001).
• Model-estimated AHI reduction from baseline was 44.1% with AD109 vs 17.6% with placebo in the intent-to-treat analysis.
• Oxygen desaturation index improved with AD109 vs placebo (treatment difference, −4.5 events/hour; P=.001). Hypoxic burden also decreased, although formal hierarchical testing had stopped before this endpoint.
• Complete disease control, defined as AHI <5 events/hour, occurred in 17.6% of participants receiving AD109 vs 9.3% receiving placebo.

PROMIS-Fatigue scores improved in both groups, but the between-group difference did not meet statistical significance in the primary analysis. Adverse events occurred in 70.8% of participants receiving AD109 and 46.7% receiving placebo. The most common events with AD109 were dry mouth, insomnia, nausea, and urinary hesitation; 21.2% discontinued AD109 because of adverse events, compared with 3.1% in the placebo group. No deaths or treatment-related serious adverse events were reported.

AD109 remains investigational. Apnimed has submitted a New Drug Application to the FDA, and the company reported that, if the application is accepted, a potential FDA target action date could fall in the first quarter of 2027.

Sources

1. American Thoracic Society. Once-night pill treats causes of airway collapse to control OSA. EurkAlert! Published May 18, 2026. Accessed May 22, 2026. https://www.eurekalert.org/news-releases/1127768
2. Apnimed Inc. Apnimed announces publication of its phase 3 SynAIRgy trial of AD109 for obstructive sleep apnea in the American Journal of Respiratory and Critical Care Medicine. PRNewswire. Published May 18, 2026. Accessed May 22, 2026. https://www.prnewswire.com/news-releases/apnimed-announces-publication-of-its-phase-3-synairgy-trial-of-ad109-for-obstructive-sleep-apnea-in-the-american-journal-of-respiratory-and-critical-care-medicine-302774259.html
3. Strollo PJ Jr, Farkas R, Taranto-Montemurro L, Cronin J, Patel SR; SynAIRgy Investigators. Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnea: a randomized phase 3 trial (SynAIRgy). Am J Respir Crit Care Med. Published online May 18, 2026. doi:10.1093/ajrccm/aamag215
4. Horner RL, Wellman DA, Sands SA, Azarbarzin A, Taranto-Montemurro L. Mechanisms of upper airway muscle control in sleep reveal therapeutic targets for obstructive sleep apnea. Am J Respir Cell Mol Biol. Published online 2026. doi:10.1093/ajrcmb/aanag089.