Mechanism and Rationale Behind AD109 for Obstructive Sleep Apnea: Patrick Strollo, MD, FACP, FCCP, FAASM

WATCH TIME: 7 minutes

"AD109 is exciting because it acts immediately by stabilizing upper airway muscles—unlike weight-based therapies, it doesn’t require time or body composition changes to work."

Obstructive sleep apnea (OSA) poses as one of the more challenging and prevalent disorders to treat, impacting up to 1 billion people globally, with higher prevalence among men and increasing risk with age and obesity. The standard of care for years has been continuous positive airway pressure (CPAP); however, adherence to CPAP devices have caused issues in the treatment paradigm. There are a number of emerging therapeutics, including AD109 (Apnimed) that are looking to provide patients with more relief.

Recently announced findings from a phase 3 trial dubbed SynAIRgy (NCT05813275) showed that AD109, a once-daily oral pill, led to significant reductions in apnea-hypopnea index (AHI) in patients with a range of OSA severities. Overall, the drug met its primary end point of AHI change relative to placebo (P = .001) over the 26-week treatment period, while maintaining a safety profile that is tolerable and easily manageable for patients. Based on the data, Apnimed, the drug manufacturers, are planning to submit a new drug application to the FDA in early 2026 for AD109 to become a potential option for patients with OSA.

Following the data release, NeurologyLive^® sat down with study investigator Patrick Strollo, MD, FACP, FCCP, FAASM, to provide an in-depth look at the rationale and implications of AD109, a combination agent of antimuscarinic aroxybutynin and atomoxetine. He spoke on how unlike weight-loss-based therapies like tirzepatide, AD109 offers immediate therapeutic effect by enhancing upper airway muscle tone during sleep, independent of body weight. Strollo, professor of medicine and clinical translational science at the University of Pittsburgh, emphasized the importance of expanding beyond CPAP as the default treatment, especially for patients who struggle with adherence or do not fit the profile for other options.

REFERENCE
1. 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. News release. Apnimed. May 19, 2025. Accessed June 2, 2025. https://apnimed.com/article/ad109phase3toplineresults/