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

On May 19, 2025, Apnimed announced that the phase 3 SynAIRgy clinical trial evaluating AD109 for obstructive sleep apnea (OSA) 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 in Seattle.

“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 HCPLive during an on-site interview.

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 (P = .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 (P < .0001) and oxygen desaturation index (P = .001).

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.

References

1. 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.

2. 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/. Accessed June 19, 2025.