The study, "Aroxybutynin and Atomoxetine (AD109) for Obstructive Sleep Apnea: A Randomized Phase 3 Trial," was published in the American Journal of Respiratory and Critical Care Medicine.

In the SynAIRgy trial, people who received AD109 experienced fewer interruptions in breathing, less oxygen deprivation, and better overall blood oxygen levels while they slept. More than 40 percent improved enough to move into a less severe OSA category, while 18 percent achieved complete disease control.

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

A Potential Alternative for People Who Cannot Use CPAP

Continuous Positive Airway Pressure (CPAP) remains the gold standard treatment for OSA, but many people have difficulty tolerating it. Dr. Strollo said AD109 could provide another option for patients who are unable or unwilling to use CPAP.

"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," he said. "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."

AD109 combines two drugs, aroxybutynin and atomoxetine. Together, they are intended to support the muscles of the throat so the airway is less likely to sag or collapse during sleep.

Breathing Interruptions Fell by About 44 Percent

Researchers conducted the six-month trial at 69 sites in the U.S. and Canada. A total of 646 adults with mild to severe OSA participated, all of whom had either refused CPAP or were unable to tolerate it.

Among patients who took AD109, the apnea-hypoxia index, which measures the number of breathing interruptions per hour, fell by about 44 percent. By comparison, the reduction was 18 percent among participants who received a placebo.

Other measures of nighttime oxygen problems also improved. These included the oxygen desaturation index (the number of times during the night that blood oxygen drops) and hypoxic burden (oxygen deficiency).

The benefits were seen across a wide variety of patients, including people with different levels of disease severity and different body types.

Side Effects and Treatment Discontinuation

AD109 also showed an acceptable safety profile, with side effects that researchers described as mild and expected. The most frequently reported side effects were dry mouth, nausea, insomnia, and difficulty urinating.

About 21 percent of patients stopped taking the treatment because of side effects.

Dr. Strollo said the clinical findings will be published alongside a companion mechanistic review by ATS in the American Journal of Respiratory Cell and Molecular Biology.

"Together, these peer-reviewed articles connect late-stage clinical outcomes with the biological mechanisms that drive the disease, targeted by the mechanism of action of AD109, providing a more complete and integrated view of OSA and strengthening confidence in the approach," he said.

FDA Review Could Come Next

AD109 has received Fast Track designation from the FDA for the treatment of OSA, reflecting the need for effective and well-tolerated drug therapies for the condition.

Apnimed has submitted its New Drug Application (NDA) for AD109 to the FDA. Based on feedback from the agency, the company expects a potential PDUFA target action date in 1Q 2027, provided the FDA accepts the NDA for review.