Latest Pharmacotherapy Developments for Sleep Apnea, with Danny Eckert, PhD

HCPLive spoke with Danny Eckert, PhD, a professor at Flinders University, about the latest pharmacotherapy developments for sleep apnea at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies in Seattle.1

For years, treatments aimed to open the narrow, collapsible upper airway that is a major cause of obstructive sleep apnea (OSA), such as continuous positive airway pressure therapy, oral appliances, and multi-level upper airway surgery. However, recently, studies discovered that non-anatomical causes, like impaired upper airway muscle function, can cause OSA.

When pharyngeal dilators do not activate enough during sleep, people may experience sleep apnea. Another non-anatomical factor leading to OSA is arousal threshold, describing how easily you wake up to a little bit of airway narrowing; light sleep also impacts sleep apnea. Respiratory control instability can also lead to OSA.

“By discovering all of these different causes, we've now been able to go in and intervene and do studies to try and rectify the root causes for the individuals involved,” Eckert said.

The US Food and Drug Administration recently approved the GLP-1 receptor agonist tirzepatide for obese individuals with sleep apnea.2

“The way that works is by making the airway less collapsible via weight loss,” Eckert said. “You take off the weight, and the upper airway becomes less collapsible, at least that's the way we think it works. So that's an important solution that's now available for that group of patients [who] are obese.”

However, he said 40% to 50% of people with sleep apnea are not obese, so tirzepatide will not help them. Non-obese patients with OSA tend to respond less to conventional therapies and have a low arousal threshold, linked to poor CPAP compliance.

“In these other groups, other things that are emerging, and the most advanced, is AD109, which is [a] recombination therapy drug approach from Apnimed,” Eckert said.

AD109 is an investigational first-in-class combination of aroxybutynin, a novel antimuscarinic, and atomoxetine, a noradrenaline reuptake inhibitor.3 The company announced topline phase 3 results for AD109, a once-daily oral pill for OSA, with the trial meeting its primary endpoint of mean change in apnea-hypopnea index (P = .001) at 26 weeks. The pivotal data showed about 25% of patients had their sleep apnea resolved, and 50% had a reduction in sleep apnea severity.

Eckert said that the benefit of AD109 was about equivalent to the benefit of tirzepatide.

Another emerging treatment he mentioned was a potassium channel blocker, targeting reflexes in the upper airway. This blocker does not numb the airway but rather resets reflex pathways. This treatment has shown success in 25% to 30% of participants in early research. Acetazolamide also shows promise in lowering the loop gain and reducing sleep apnea by 40% to 50%.

“This is a very exciting time for the field,” Eckert said. “I've been in this field for 25 years now, and there's long been a quest to come up with a drug-based therapy for sleep apnea, and through learning more about the neurology of this very common chronic respiratory disorder, we've been able to finally have some targets for pharmacotherapy.”

References

1. Eckert D. Latest Insights into the Development of Pharmacotherapy for Sleep Apnea. Presented at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies, on Monday, June 9, in Seattle.

2. Iapoce, C. FDA Approves Tirzepatide for Obstructive Sleep Apnea in Obesity. HCPLive. December 20, 2024. https://www.hcplive.com/view/fda-approves-tirzepatide-for-obstructive-sleep-apnea-in-obesity. Accessed June 10, 2025.

3. Apnimed Announces Positive Topline Results in the First Landmark Phase 3 Clinical Trial of AD109, an Investigational Once-daily Oral Pill for Obstructive Sleep Apnea. PR Newswire. May 19, 2025. https://www.prnewswire.com/news-releases/apnimed-announces-positive-topline-results-in-the-first-landmark-phase-3-clinical-trial-of-ad109-an-investigational-once-daily-oral-pill-for-obstructive-sleep-apnea-302458517.html. Accessed June 10, 2025.