Danny Eckert, PhD

HCPLive Five at SLEEP 2025 

 SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies,

 from June 9 – 11th in Seattle, Washington, to share new sleep medicine data.

As a part of HCPLive’s on-site coverage, the editorial team conducted > 15 interviews on various topics, from new pharmacotherapy treatments for OSA and AI in sleep medicine to changes to the restless legs syndrome (RLS) guidelines and the association between napping and mortality risk in older adults.

In this edition of the HCPLive Five, the team captured the top 5 interviews at the meeting, featuring research on a VeNS device for insomnia and PTSD, latest pharmacotherapy developments for sleep apnea, new RLS guidelines, the link between naps and mortality risk, and AD109 for obstructive sleep apnea (OSA).

VeNS Device Improves PTSD, Insomnia Symptoms in RCT, with Peter Colvonen, PhD

Peter Colvonen, PhD, an associate clinical professor at the University of California, San Diego, presented results from a randomized controlled trial showing that vestibular nerve stimulation (VeNS) significantly improved PTSD and insomnia symptoms. The 12-week trial involved over 380 adults with PTSD, many of whom face years-long waits for 1-on-1 therapy.

VeNS, a non-invasive, at-home device, led to significantly greater reductions in PTSD and Insomnia Severity Index scores compared to a sham. Colvonen emphasized its potential as an interim solution for patients stuck on long waitlists, highlighting VeNS as a scalable option to stabilize symptoms until gold-standard care becomes available.

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

Danny Eckert, PhD, a professor at Flinders University, highlighted emerging pharmacotherapies for obstructive sleep apnea (OSA), addressing both anatomical and non-anatomical causes. The FDA-approved GLP-1 agonist tirzepatide helps reduce OSA in obese patients through weight loss.

For non-obese individuals, AD109, a combination of aroxybutynin and atomoxetine, showed promise in a phase 3 trial, resolving OSA in 25% of patients. Eckert also discussed potassium channel blockers that reset airway reflexes and acetazolamide, which lowers loop gain and reduces OSA severity. These advances mark a shift toward personalized, drug-based OSA treatments, especially for patients who struggle with traditional therapies like CPAP.

RLS Guidelines Advise Against Dopamine Agonists, With John Winkelman, MD, PhD

John Winkelman, MD, PhD, chief of the sleep disorders clinical research program at Massachusetts General Hospital, discussed the AASM’s updated restless legs syndrome (RLS) guidelines, which now advise against routine use of dopamine agonists due to high augmentation risk. Up to 50% of patients on these drugs may experience symptom worsening over five years. The guidelines recommend iron therapies and alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) instead.

Winkelman emphasized identifying and managing exacerbating factors like antidepressants, antihistamines, or sleep apnea. He advises a slow, careful taper of dopamine agonists over 6–12 months, warning patients of temporary worsening but long-term improvement once off the medication.

Naps at Noon Linked to Mortality Risk in Older Adults, with Chenlu Gao, PhD

Chenlu Gao, PhD, from Massachusetts General Hospital and Harvard Medical School, presented findings linking longer, irregular, and early afternoon naps to increased all-cause mortality in middle-to-older adults. Using UK Biobank data from over 86,000 participants, the study found that greater nap duration, high day-to-day variability, and naps between 11 am–3 pm were associated with higher mortality risk over an 8-year follow-up.

Gao emphasized the study was observational and not causal—napping patterns may reflect underlying health issues like sleep disorders or chronic illness. She advised clinicians to address root causes of excessive napping rather than eliminating naps entirely.

AD109 Improves OSA in Phase 3 SynAIRgy Trial, With Patrick Strollo, MD

Patrick Strollo, MD, from the University of Pittsburgh Medical Center, presented phase 3 SynAIRgy trial results showing that AD109, a once-daily oral neuromuscular modulator, significantly improved obstructive sleep apnea (OSA). In the 26-week trial of 646 participants intolerant of CPAP, AD109 reduced apnea-hypopnea index (AHI) by 55.6% and improved oxygenation measures. More than half of participants had reduced OSA severity, and 22.3% achieved full disease control (AHI < 5).

AD109, a first-in-class combination of aroxybutynin and atomoxetine, works by enhancing upper airway muscle tone during sleep. Apnimed plans to submit an FDA application in early 2026, with additional phase 3 data expected later in 2025.

Articles

Sleep experts gathered at SLEEP 2025 to discuss advancements in sleep medicine, including new treatments and guidelines. Key topics included a VeNS device for PTSD and insomnia, pharmacotherapy for sleep apnea, updated RLS guidelines, and the link between napping and mortality risk. The VeNS device showed promise in reducing PTSD and insomnia symptoms, while new pharmacotherapies like AD109 and tirzepatide offered hope for OSA patients. Updated RLS guidelines advised against dopamine agonists, and research linked irregular naps to increased mortality risk, emphasizing the need to address underlying health issues.

Check out the top 5 interviews from SLEEP 2025.

spoke with Danny Eckert, PhD, a professor at Flinders University, about the latest pharmacotherapy developments for 

 SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies 

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.

“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.

 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 (

 = .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.”

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.

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

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

Videos

At SLEEP 2025, Danny Eckert, PhD, discussed new drug therapies for OSA, including tirzepatide, AD109, potassium channel blockers, and acetazolamide.
