Investigational Oral AD109 Reduces Sleep Apnea Severity by 44%

Results from a large phase 3 clinical trial (NCT05813275) presented at the 2026 American Thoracic Society (ATS) International Conference show that a once nightly oral medication significantly improved obstructive sleep apnea (OSA) in patients who could not or would not use continuous positive airway pressure (CPAP), the device most commonly ordered to treat the condition.¹

The drug, AD109, is designed to treat OSA by targeting the neuromuscular problems that contribute to airway collapse during sleep. Findings from the trial, known as SynAIRgy, were also published in the American Journal of Respiratory and Critical Care Medicine.²

An Alternative for Patients Who Reject CPAP

OSA is a common condition in which the airway narrows or closes during sleep, most often because soft tissue in the throat and tongue relaxes and collapses. It can produce loud snoring, gasping or choking sounds, and repeated pauses in breathing overnight, along with daytime fatigue, morning headaches, and difficulty concentrating. Left untreated, OSA is linked to hypertension, heart disease, stroke, diabetes, and a higher risk of accidents caused by daytime sleepiness.^3,4

CPAP remains the device most commonly prescribed for OSA, working by delivering pressurized air that keeps the airway open. But many patients cannot tolerate the mask or refuse the therapy altogether, leaving a substantial share of diagnosed patients without effective treatment.³

"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," Patrick J. Strollo Jr., MD, first author of the SynAIRgy trial and a sleep medicine physician affiliated with the University of Pittsburgh, said in a news release from the American Thoracic Society.¹ "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."

Trial Design and Efficacy Results

SynAIRgy was a randomized, double-blind, placebo-controlled, 26-week trial conducted at 69 centers across the United States and Canada. Investigators enrolled 646 adults with OSA, with 615 included in the main efficacy cohort (302 receiving AD109 and 313 receiving placebo). Participants had a median age of 58 years (range, 24 to 87), and 49.3% were female.²

The population had a median body mass index of 32.4 kg/m² (range, 18.5 to 42.0) and a median baseline apnea-hypopnea index (AHI) of 19.6 events per hour, with 34.8% classified as mild, 42.1% as moderate, and 23.1% as severe OSA. Nearly all participants had either failed CPAP therapy (66.8% were intolerant) or refused it outright (33.3%).²

Participants took AD109—a fixed-dose combination of aroxybutynin 2.5 mg and atomoxetine 75 mg—or placebo once daily at bedtime. By week 26, AHI fell by 3.3 events per hour in the AD109 group (95% CI, –5.1 to –1.5) compared with an increase of 0.7 events per hour in the placebo group (95% CI, –1.0 to 2.4), a treatment difference of 4.0 events per hour (95% CI, –6.4 to –1.6; P = .001). Expressed as a geometric mean reduction, AHI dropped 44.1% with AD109 versus 17.6% with placebo (P <.0001).²

Secondary measures moved in the same direction. The oxygen desaturation index improved by 3.7 events per hour with AD109 versus 0.9 events per hour with placebo (P = .001), and hypoxic burden fell 44.7% with AD109 versus 8.5% with placebo, though that comparison was a nominal finding after formal statistical testing was halted under the trial's prespecified hierarchical testing approach.²

More than 40% of AD109 patients (41.8%) improved into a less severe OSA category, compared with 33.6% on placebo, and 17.6% of AD109 patients achieved complete disease control, defined as an AHI below 5 events per hour, versus 9.3% on placebo (P = .012). Improvement was apparent as early as week 4, and benefits held up across sexes, OSA severity categories, and body mass index classes.²

Safety and Tolerability

AD109 was not without tradeoffs. Among AD109 recipients, 21.2% (67 of 318) discontinued treatment because of adverse events, compared with 3.1% (10 of 319) on placebo. The most common adverse events reported were dry mouth, nausea, insomnia, and urinary hesitation.^1,2

No serious treatment-related adverse events were reported, and among participants who remained on therapy, adherence was similar between arms—95.7% for AD109 completers versus 95.5% for placebo completers. Overall, 84.6% of participants completed the trial (83.3% of the AD109 group and 85.9% of the placebo group).²

The study authors also noted limitations. An exploratory cohort examining concomitant use of glucagon-like peptide-1 receptor agonists had low enrollment and was not included in the reported results, and 1 trial site was terminated for noncompliance with Good Clinical Practice standards, resulting in the exclusion of 16 participants from the efficacy analyses.²

"These results provide encouraging evidence that targeting neuromuscular dysfunction can translate into meaningful clinical outcomes, aligning with our evolving understanding of the disease biology," Strollo said in the news release.¹

What It Means for Pharmacists

AD109 received fast track designation from the FDA for the treatment of OSA, and the drug's sponsor has submitted an NDA to the agency. Based on feedback from the FDA, the sponsor expects a potential PDUFA target action date in the first quarter of 2027, provided the agency accepts the NDA for review. AD109 is not yet FDA approved and is not currently available for pharmacists to dispense.¹

If approved, AD109 would give pharmacists and prescribers an oral option to discuss with the large share of OSA patients who reject or cannot tolerate CPAP—a gap the trial's investigators specifically framed the drug as addressing. The adverse effect profile reported in SynAIRgy is the kind of information pharmacists will need to counsel on if the drug reaches the market, alongside the once nightly dosing schedule that will factor into adherence conversations.²

For now, pharmacists fielding questions from patients who have seen coverage of the trial can accurately describe AD109 as investigational, with an FDA decision not expected before early 2027 at the soonest.¹

REFERENCES

1. American Thoracic Society. Goodbye CPAP? New sleep apnea pill cuts breathing events by 44%. News release. ScienceDaily. August 31, 2026. Accessed September 1, 2026. https://www.sciencedaily.com/releases/2026/08/260831015203.htm

2. 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. 2026;212(7):1569-1584. doi:10.1093/ajrccm/aamag215

3. American Thoracic Society. What is obstructive sleep apnea in adults? American Thoracic Society. Accessed September 1, 2026. https://site.thoracic.org/advocacy-patients/patient-resources/what-is-obstructive-sleep-apnea-in-adults

4. Mayo Clinic Staff. Sleep apnea - symptoms and causes. Mayo Clinic. Accessed September 1, 2026. https://www.mayoclinic.org/diseases-conditions/sleep-apnea/symptoms-causes/syc-20377631