Apnimed reported that investigational oral therapy AD109 met the primary endpoint in the Phase 3 SynAIRgy trial, reducing apnea-hypopnea index by 55.6% versus placebo in adults with obstructive sleep apnea.
Written By: Mahathi Palivela, PharmD
Reviewed By: Pharmacally Editorial Team
Apnimed announced that its investigational oral therapy AD109 met the primary endpoint in the Phase 3 SynAIRgy trial in adults with obstructive sleep apnea (OSA), demonstrating a 55.6% reduction in apnea-hypopnea index (AHI) at week 26 compared with placebo using the ≥4% desaturation criterion for hypopneas (p≤0.0001).
The results were published in the American Journal of Respiratory and Critical Care Medicine alongside a companion mechanistic review article in the American Journal of Respiratory Cell and Molecular Biology.
AD109 is a fixed-dose combination of aroxybutynin 2.5 mg and atomoxetine 75 mg designed to improve oxygenation during sleep and target neuromuscular dysfunction associated with upper airway collapse in OSA. The companion review article highlighted neuromuscular dysfunction as a key driver of OSA and outlined the biological rationale supporting AD109’s mechanism of action.
The SynAIRgy trial also showed significant improvements in oxygenation measures, including a 60.5% reduction in geometric mean hypoxic burden and a mean reduction of 6.5 events per hour in oxygen desaturation index versus placebo (p<0.0001 for both). Among participants receiving AD109, 39.6% achieved at least a 50% reduction in AHI, while 22.3% reached disease control defined as AHI below five events per hour. Benefits were observed across mild, moderate, and severe OSA populations and in participants with and without obesity. Improvements appeared as early as week four and were maintained through week 26.
AD109 was generally well tolerated. The most common adverse events were dry mouth, insomnia, and nausea, consistent with earlier clinical studies. No treatment-related serious adverse events were reported.
Patrick J. Strollo Jr., M.D., study chair of the SynAIRgy trial at the University of Pittsburgh School of Medicine, said the findings support neuromuscular dysfunction as an important driver of OSA and showed that targeting this pathway can improve airway obstruction and oxygenation.
Neomi Shah, MD, MPH, MSc, ATSF, of the American Thoracic Society, said the study advances efforts toward more personalized treatment approaches for OSA.
The randomized, double-blind, placebo-controlled SynAIRgy trial (NCT05813275) enrolled 646 adults with OSA across 69 centers in the United States and Canada. Participants who had failed or refused positive airway pressure (PAP) therapy were randomized to receive AD109 or placebo once nightly for six months, highlighting the unmet need for alternative treatment options in OSA.
AD109 has received Fast Track designation from the U.S. Food and Drug Administration for OSA treatment. Apnimed has submitted a New Drug Application for AD109 and expects a potential FDA action date in the first quarter of 2027, pending NDA acceptance for review. If approved, AD109 could become the first oral pharmacologic therapy for OSA.
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About the Writer
Mahathi Palivela (LinkedIn) is pursuing PharmD and has a strong interest in Clinical Pharmacy and Patient safety. She is passionate about handling and analyzing patient data, and translating clinical insights into clear, meaningful summaries. She aims to apply this interest in Medical Writing and Pharmacovigilance, focusing on improving patient outcomes through careful data interpretation and communication.