Obstructive Sleep Apnea (OSA) remains a widespread yet under-treated condition, affecting millions globally. Traditional treatments such as CPAP therapy, while effective, are often hindered by poor patient adherence due to discomfort and lifestyle disruption. In response to this unmet need, Apnimed’s novel investigational therapy, AD109, offers a compelling oral alternative for OSA. AD109 is a combination of atomoxetine, a norepinephrine reuptake inhibitor, and aroxybutynin, a muscarinic antagonist. This dual mechanism is designed to address upper airway collapsibility—a key pathophysiological feature of OSA—without requiring mechanical intervention. A recently published article in the American Journal of Respiratory and Critical Care Medicine, AD109 demonstrated robust efficacy and an acceptable safety profile over a 1-month treatment period in patients with mild to severe OSA.
The primary endpoint, AHI4 (apnea–hypopnea index using a 4% desaturation criterion), was significantly reduced by 45% in patients treated with AD109 compared to placebo. Impressively, 44% of participants who received AD109 achieved a ≥50% reduction in AHI4, and 42% reached an AHI4 below 10 events per hour—a level associated with minimal disease severity. The 2.5/75 mg dose also improved subjective fatigue scores, as measured by the PROMIS fatigue scale, suggesting broader functional benefits beyond respiratory endpoints.
Safety and tolerability remain critical for any chronic therapy, particularly for OSA, a condition often accompanied by cardiovascular comorbidities. AD109 was generally well tolerated, with the most frequent adverse events being dry mouth, insomnia, and urinary hesitancy—consistent with the known side-effect profiles of its constituent drugs. Notably, insomnia and sleep disturbance were more prevalent with atomoxetine alone (Ato75), which led to higher study discontinuation rates. In contrast, AD109 showed fewer sleep-related side effects, reinforcing the importance of the combination’s synergistic design.
Interestingly, while both REM and NREM sleep demonstrated improvements in AHI4, the reduction in REM sleep did not reach statistical significance. The reduction in REM sleep, a known effect of atomoxetine, appeared to attenuate over time, suggesting a potential adaptation with chronic dosing.
Importantly, the therapeutic benefit of AD109 was most pronounced in patients with mild to moderate OSA. Among those with severe disease (AHI4 >30), only 7% reached an AHI4 <10, compared to 77% of those with mild OSA and 42% with moderate disease.
Dr. Larry Miller, Chief Executive Officer of Apnimed, commented: “The positive results from our Phase 3 SynAIRgy trial bring us closer to realizing our vision of offering a simple, safe, and effective oral drug — one that is grounded in science, driven by unmet need, and centered on people with OSA.” AD109 represents a promising advancement toward a patient-friendly, pharmacological solution for OSA—a condition long dominated by devices. With continued development and regulatory success, it may well usher in a new era of OSA care.
Sources: American Journal of Respiratory and Critical Care Medicine, Apnimed
