Patrick J. Strollo, MD, from the University of Pittsburgh Medical Center

Patrick J. Strollo, MD

What the Phase 3 AD109 Data Mean for Sleep Apnea, With Patrick John Strollo, MD 

Patrick John Strollo, MD, study author and sleep medicine physician at the University of Pittsburgh Medical Center, spoke with 

 at the American Thoracic Society (ATS) conference about key insights into the 

, including patient-reported outcomes, tolerability, and where AD109 might fit in the OSA treatment landscape if approved.

On the question of fatigue outcomes, Strollo noted that the primary analysis included the full trial population, as many of whom had mild OSA and relatively few fatigue complaints at baseline. When the analysis was narrowed to more symptomatic patients, specifically those with an Epworth Sleepiness Scale score above 10, the improvement in PROMIS fatigue scores was more pronounced. He also noted that fatigue can be difficult to measure in a society with widespread chronic sleep deprivation; AD109 may reduce sleep-disordered breathing, but it cannot reverse years of accumulated sleep debt.

Regarding the approximately 21–25% discontinuation rate due to adverse events, Strollo explained that the 3 main culprits, such as insomnia, dry mouth, and GI side effects, are consistent with the known profiles of both aroxybutynin and atomoxetine. He noted that the trial did not screen carefully for comorbid insomnia at enrollment, and patients with underlying insomnia may have been particularly susceptible to those effects. Patients who remained on treatment, however, tended to stay on drug and derive meaningful benefit.

Strollo highlighted the trial's notably broad population as a strength, 74% of participants had mild-to-moderate OSA, roughly a third were non-obese, and no specific signal emerged favoring the drug in any particular age, weight, demographic, or severity subgroup. He characterized AD109 as a first-in-class agent that, if approved, would represent another tool in the toolbox, particularly for the large population of patients who cannot tolerate or refuse PAP therapy and currently have limited options.

Disclosures: Strollo served as a consultant for Apnimed, Inspire Medical Systems, Cryosa, Somnomed, Philips Respironics, WisperSom, Biologix, Emmi Solutions, Zoll Medical Corporation, Restora, XII Medical and has received grant support through his institution from ResMed, Inspire Medical Systems, and Zoll Medical. He is also a non-Executive Director of Belluscura.

Patel S, Farkas R, Pho H, et al. (Poster Board # P194) Aroxybutynin and Atomoxetine (AD109) in Obstructive Sleep Apnea: A Pooled Analysis of the SynAIRgy and LunAIRo Phase 3 Trials. Poster presented at ATS 2026 on May 17.

Strollo P. AD109 Effective as Oral Agent for Obstructive Sleep Apnea, With Patrick John Strollo, MD. HCPLive. May 19, 2026. Accessed May 20, 2026. 

https://www.hcplive.com/view/ad109-effective-oral-agent-obstructive-sleep-apnea-patrick-john-strollo-md

Videos

This interview at ATS highlights key takeaways regarding new phase 3 data on AD109 for obstructive sleep apnea (OSA).

AD109 Shows Promise as Oral Agent for Obstructive Sleep Apnea, With Patrick John Strollo, MD

A once-nightly oral pill called AD109 demonstrated statistically significant and clinically meaningful 

 improvements in the largest pharmacotherapy clinical development program ever conducted for the condition.

, drawn from a pooled analysis of two phase 3 trials, SynAIRgy and LunAIRo, were presented at the 2026 American Thoracic Society (ATS) International Conference.

 Patrick John Strollo, MD, study author and a sleep medicine physician at the University of Pittsburgh Medical Center, spoke about AD109 and its efficacy.

“AD109, which is an investigational drug and which we studied in the SynAIRgy trial, offers another tool in the toolbox, and it's a first in class drug that is a neuromuscular modulator to address the problem with sleep apnea, which is airway obstruction,” Strollo explained.

AD109, he noted, combines 2 medications: aroxybutynin and atomoxetine. They are designed in this agent to work together to address the neuromuscular root causes of OSA, specifically the collapse of throat muscles during sleep that repeatedly obstructs the airway.

Strollo and his team’s 2 randomized, double-blind, placebo-controlled phase 3 trials assessed adults with mild-to-severe OSA who had failed or refused CPAP. They spanned a broad range of severity levels and body types. AD109 produced a model-estimated 39.3% reduction in the apnea-hypopnea index (AHI) from baseline in the pooled analysis, compared to 12.6% with placebo.

Additionally, Strollo et al found 28% of those given AD109 attained a 50% or greater AHI reduction. A significantly higher proportion reached complete disease control. AD109 also diminished patients’ hypoxic burden by 41.6% versus 9.9% with placebo, and those showing excessive daytime sleepiness reported meaningful improvements in fatigue and sleep impairment scores. Benefits were also shown by Strollo and coauthors to be consistent across severity levels and body types.

Apnimed has already submitted a New Drug Application to the US Food and Drug Administration (FDA), which has granted AD109 Fast Track designation. A potential PDUFA target action date is slated for the first quarter of 2027.

Once-nightly pill treats causes of airway collapse to control OSA. American Thoracic Society. May 18, 2026. Accessed May 19, 2026. 

https://www.eurekalert.org/news-releases/1127768

This interview at ATS 2026 highlights notable findings on the once-nightly oral pill, AD109, in obstructive sleep apnea (OSA).

AD109 Effective as Oral Agent for Obstructive Sleep Apnea, With Patrick John Strollo, MD

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.

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

On May 19, 2025, Apnimed announced that the phase 3 SynAIRgy clinical trial evaluating AD109 for 

 met its primary endpoint: mean change in apnea-hypopnea index (AHI) at 26 weeks. These topline results, similar to those from a previous 4-week MARIPOSA phase 2b clinical trial, were presented at 

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

“The interesting thing about A109 [is] it's the first in class drug which modulates hypoglossal motor nerve function, and the hypoglossal nerve is one of the main nerves that innervates the upper air wiper,” investigator Patrick J. Strollo, MD, from the University of Pittsburgh Medical Center, told 

OSA occurs in 1 billion people worldwide and is caused by 2 overlapping mechanisms: neuromuscular dysfunction during sleep and predisposing anatomic abnormalities. AD109 (aroxybutynin 2.5mg/atomoxetine 75mg), a first-in-class, anti-apneic neuromuscular modulator, targets the root cause of OSA by increasing upper airway muscle tone during sleep.

SynAIRgy, a randomized, double-blind, placebo-controlled, parallel-arm 6-month clinical trial, evaluated a fixed dose of AD109 in 646 participants from 73 centers with OSA who are intolerant of or currently refuse continuous positive airway pressure (CPAP) therapy. Participants were randomized 1:1 to receive AD109 or placebo and instructed to take their treatment once daily before bedtime.

“Many trials for sleep apnea… tend to be focused on middle-aged men because they're easy to recruit, but we really made sure that we looked at a variation in severity of disease, as well as a more generalized sample of the patient population,” Strollo said.

SynAIRgy met its primary endpoint: mean change in the AHI at 26 weeks in people with mild, moderate, and severe OSA (

 = .001). Participants on AD109 achieved a mean AHI reduction of 55.6% from baseline.

The trial also met its secondary and exploratory endpoints, showing participants on AD109 had meaningful improvements in oxygenation, as assessed by hypoxic burden (

 < .0001) and oxygen desaturation index (

Moreover, 51.2% of participants on AD109 experienced a reduction in OSA disease severity, and 22.3% of participants achieved complete OSA disease control (AHI < 5 events/ hour).

Apnimed plans to submit a New Drug Application (NDA) for AD109 to the US Food and Drug Administration (FDA) by early 2026. Topline data from the second phase 3 LunAIRo trial, a 1-year study of AD109 in adults with OSA, is expected to be announced in Q3 2025.

“The main thing to keep in mind, and why this is so exciting, is this is a first-in-class drug to treat obstructive sleep apnea, really targeting neuromuscular [functions], that is really transformational,” Strollo said.

Strollo P, Cronin J, Pho H. DEMOGRAPHIC AND BASELINE DISEASE CHARACTERISTICS OF SYNAIRGY: A PHASE 3 TRIAL OF AROXYBUTYNIN AND ATOMOXETINE (AD109) IN OBSTRUCTIVE SLEEP APNEA. Presented at SLEEP 2025 the 39th annual meeting of the Associated Professional Sleep Societies from June 8 – 11th in Seattle.

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. Apnimed. May 19, 2025. 

https://apnimed.com/article/ad109phase3toplineresults/

At SLEEP 2025, HCPLive spoke to Strollo about the phase 3 SynAIRgy trial which evaluated AD109, a first-in-class, once-daily oral neuromuscular modulator, for OSA.