The SynAIRgy trial, a multicenter randomized Phase 3 study of 646 adults with mild-to-severe OSA who refused or could not tolerate CPAP, demonstrated that AD109 (aroxybutynin-atomoxetine) reduced AHI by 44% versus 18% on placebo while improving hypoxic burden and oxygen desaturation index across BMI and severity strata. This RCT design, conducted at 69 North American sites over six months, provides higher-grade evidence than prior small observational or crossover studies of noradrenergic-antimuscarinic combinations. What original coverage overlooked is the broader pattern: real-world CPAP adherence hovers near 50% in large registries, leaving cardiovascular and metabolic risk unaddressed, whereas an oral agent targeting genioglossus tone during REM and NREM sleep could close that gap. Earlier mechanistic work, such as the 2023 AJRCCM paper on atomoxetine-oxybutynin effects on upper-airway dilator activity, already predicted these outcomes; the current results validate translation from physiology to clinical endpoints. Limitations include 21% discontinuation from anticholinergic effects and industry sponsorship by Apnimed, which raises standard questions about long-term cardiovascular safety not fully captured in six-month data. If approved under Fast Track, AD109 would mark the first FDA-recognized pharmacologic therapy for OSA's core neuromuscular pathophysiology rather than its downstream hypoxia.