After a successful phase 3 clinic trial, a sleep apnoea pill is awaiting fast-tracked approval from the US Food & Drug Administration, a move that could bring relief to the almost 1bn people worldwide who are affected by this disorder – as well as those who sleep next to them.
The hallmark of obstructive sleep apnoea is repeated blockage of breathing during sleep, which can lead to daytime tiredness, headaches and snoring. Long-term, these nightly episodes that leave patients gasping for air can have serious impacts on their cardiovascular system, brain function and other aspects of their health.
Many patients treated for obstructive sleep apnoea use a CPAP (continuous positive airway pressure) machine to keep their upper airway open throughout the night.
But while these machines are effective, they're not exactly comfortable or portable, and many patients simply abandon treatment because of the inconvenience and discomfort.
Patrick John Strollo, a sleep medicine physician at the University of Pittsburgh Medical Centre in the US, said most diagnosed obstructive sleep apnoea patients are going untreated or undertreated.
“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,” he said.
Strollo and colleagues recently completed a phase 3 clinical trial for a drug called AD109, to be taken nightly.
They enrolled 646 patients from across America and Canada who had been diagnosed with mild to severe obstructive sleep apnoea, but who either couldn’t tolerate or had refused to use a CPAP machine.
Participant were randomly assigned to take either the drug, AD109, or a placebo, but were unaware of which pill they had been given.
They took the pill nightly over 26 weeks, with the first week at a half-dose. By week 26, Strollo and team hoped, the group taking AD109 should start showing some improvements.
Success was measured using a system called the apnoea-hypopnoea index (AHI), which is standard for assessing obstructive sleep apnoea severity.
It brings together the average number of apnoeas (pauses in breathing) and hypopnoeas (reduced breathing with insufficient oxygen) that a patient experiences throughout the night.
For patients taking AD109, their index fell by around 44% across the trial period, while the placebo group’s indices dropped by around 18% on average.
By week 26, almost 42% of participants taking the drug had moved into a lower severity category – and nearly 18% stopped experiencing obstructive sleep apnoea altogether.
Patients experienced only a few mild side effects, including dry mouth, nausea and insomnia, but these were expected, since the drug's components are well-understood and used to treat other conditions.
The pill works by pairing aroxybutynin, which reduces activation of the parasympathetic nervous system, and atomoxetine, a drug better known for treating ADHD.
According to an accompanying review of the drug’s mechanism, this combo is “designed to counteract sleep-related withdrawal of excitatory noradrenergic drive and rapid eye movement (REM)–related muscarinic inhibition at the hypoglossal motor nucleus”.
In other words, it stops the brain from dropping the upper airway muscles during sleep.
The US Food and Drug Administration has fast-tracked approval for AD109, with the regulator’s decision expected in 2027.
And it’s not the only alternative to CPAP machines in the pipeline. Another recent clinical trial has found success in repurposing epilepsy medicine, and GLP-1 drugs have proved effective for those whose apnoeas are related to obesity.
At the more experimental end, a technique that involves implanting electrodes into the tongue has shown promise in early trials. Scientists even think blowing on a conch shell could help tone the muscles responsible.
But pharmaceutical options, like AD109, may turn out to be a convenient solution for patients hoping to free themselves from the CPAP machine.
“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.
The results were published in the American Journal of Respiratory and Critical Care Medicine.
Study details
Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnoea: a randomised phase 3 trial (SynAIRgy)
Patrick J Strollo, Ron Farkas, Luigi Taranto-Montemurro et al.
Published in the American Journal of Respiratory and Critical Care Medicine on 18 May 2026
Abstract
Rationale
Many patients with obstructive sleep apnea (OSA) are unable to tolerate long-term positive airway pressure (PAP) therapy, highlighting the need for alternative treatments. AD109 (investigational fixed-dose oral combination of aroxybutynin 2.5 mg/atomoxetine 75 mg) is designed to target neuromuscular dysfunction in OSA.
Objectives
To evaluate the efficacy/safety of AD109 over 6 months in a diverse OSA population unable to use PAP.
Methods
SynAIRgy enrolled adults with mild-to-severe OSA who were intolerant to or refused PAP therapy into a randomised, double-blind, placebo-controlled, 26-week parallel-arm trial of AD109 vs placebo across 69 centers. The primary efficacy endpoint was change from baseline to week 26 in apnea–hypopnea index (AHI). Key secondary endpoints were oxygen desaturation index (ODI), Patient-Reported Outcomes Measurement Information System (PROMIS)–Fatigue T-score, hypoxic burden (HB), PROMIS-Sleep Impairment T-score, and proportion of participants with ≥50% AHI reduction.
Measurements and Main Results
A total of 646 eligible participants (median age 58 years, 49.3% female, median body mass index 32.4 kg/m2) were randomised. Median baseline AHI was 19.6 events/hour with 35% mild, 42% moderate, and 23% severe OSA. At week 26, mean AHI treatment difference was −4.0 events/hour (95% CI, −6.4 to −1.6; P = .001), representing a model-estimated 44.1% vs 17.6% decrease from baseline (P <.0001). AD109 demonstrated improvements in ODI and HB at week 26 vs placebo; however, no statistically significant difference was observed for PROMIS-Fatigue. Overall, 21.2% of participants on AD109 and 3.1% on placebo discontinued therapy due to adverse events. The most common adverse events with AD109 were dry mouth, nausea, insomnia, and urinary hesitation, with no serious treatment-related adverse events.
Conclusions
AD109 significantly improved airway obstruction and oxygenation at 26 weeks across a broad range of patients unable to use PAP, suggesting that AD109 could become a potential treatment option for patients with OSA.
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