Once-Nightly AD109 Pill Effective for Patients with Obstructive Sleep Apnea (OSA)

A once-nightly oral pill called AD109 has demonstrated statistically significant and clinically meaningful improvements in obstructive sleep apnea (OSA) in the largest pharmacotherapy clinical development program ever conducted for the condition.1,2

These results were from a pooled analysis of a pair of phase 3 trials, SynAIRgy and LunAIRo. They were presented at the 2026 American Thoracic Society (ATS) International Conference. AD109 is an investigational oral tablet designed to combines 2 agents: aroxybutynin (2.5 mg), a novel antimuscarinic agent, and atomoxetine (75 mg), a selective norepinephrine reuptake inhibitor.

“These results provide encouraging evidence that targeting neuromuscular dysfunction can translate into meaningful clinical outcomes, aligning with our evolving understanding of the disease biology,” first author Patrick John Strollo, MD, a sleep medicine physician at the University of Pittsburgh Medical Center, said in a statement.2

Together, aroxybutynin and atomoxetine both help to address the neuromuscular root causes of OSA, specifically, the sagging or collapse of the patient’s throat muscles as they sleep leading to repeated airway obstruction and breathing issues. AD109’s mechanism-based approach makes the treatment the first specifically designed for targeting OSA at its underlying physiological level, as opposed to serving as a mechanical workaround like continuous positive airway pressure (CPAP).

The pair of randomized, double-blind, placebo-controlled phase 3 trials involved recruitment of 1299 adults total who had mild-to-severe OSA and had either failed or refused CPAP therapy. The investigators looked at a range of OSA severity levels and body types. The SynAIRgy trial ran for 26 weeks across 69 US and Canadian sites, while LunAIRo extended to 51 weeks.

Key Efficacy Findings

Strollo and colleagues’ primary measure of efficacy was the apnea-hypopnea index (AHI). In the team’s pooled analysis, individuals on AD109 experienced a model-estimated 39.3% reduction in their AHI levels from the point of baseline, compared to only 12.6% among those on a placebo.

The SynAIRgy trial alone showed an approximately 44% AHI reduction versus 18% with placebo. Nearly 28% of those on AD109 attained a 50% or greater reduction in their AHI scores. Additionally, Strollo et al found a significantly higher proportion achieved complete disease control versus the placebo arm of the study. More than 40% of subjects saw overall OSA severity improve.

Outside of breathing interruptions, AD109 also meaningfully diminished hypoxic burden, the cumulative oxygen deficiency experienced during sleep, by 41.6% versus 9.9% with placebo. Among those with excessive daytime sleepiness at baseline, the medication also led to substantial fatigue and sleep impairment improvements. In 1 notable finding, these effects were consistent across severity levels and body types, suggesting AD109’s broad potential.

Safety and Tolerability of AD109

AD109 was generally shown to be well-tolerated, with most treatment-emergent adverse events (AEs) characterized by Strollo and coauthors as mild. The most frequently reported side effects included insomnia, dry mouth, nausea, urinary hesitation, somnolence, and constipation. They found about 21% of patients in the SynAIRgy trial discontinued due to side effects, and 35.2% discontinued treatment overall in the pooled analysis by the 26-week mark, compared to the 15.5% discontinuation rate in the placebo arm.

AD109 has been given an FDA Fast Track designation. The treatment’s developer, Apnimed, has submitted a New Drug Application to FDA officials, with a potential PDUFA target action date slated for the first quarter of 2027, pending FDA acceptance of the application for review.

References

1. Patel S, Farkas R, Pho H, et al. (Poster Board # P194) Aroxybutynin and Atomoxetine (AD109) in Obstructive Sleep Apnea: A Pooled Analysis of the SynAIRgy and LunAIRo Phase 3 Trials. Poster presented at ATS 2026 on May 17.

2. Once-nightly pill treats causes of airway collapse to control OSA. American Thoracic Society. May 18, 2026. Accessed May 19, 2026. https://www.eurekalert.org/news-releases/1127768.