Phase 3 Trial Demonstrates Efficacy of First Oral Treatment for Obstructive Sleep Apnea

Results of the phase 3 LunAIRo clinical trial (NCT05811247) showed that treatment with AD109 (aroxybutynin 2.5 mg/atomoxetine 75 mg; Apnimed, Cambridge MA), an oral, anti-apneic neuromuscular modulator for the treatment of people with obstructive sleep apnea (OSA), significantly reduced airway obstruction compared with placebo. The results of LunAIRo were consistent with those of the phase 3 SynAIRgy clinical study (NCT05813275), and if approved, AD109 may offer a less invasive alternative for people with OSA unable to tolerate continuous positive airway pressure (CPAP). In a statement from Apnimed, the company announced plans to file a New Drug Application (NDA) with the Food and Drug Administration (FDA) in early 2026.

The 12-month, randomized, double-blind, placebo-controlled LunAIRo trial was conducted across 64 centers in the United States and included 660 adults with mild, moderate, or severe OSA who refused or were intolerant of CPAP therapy. Participants were randomly assigned 1:1 to receive AD109 at a fixed dose combination of aroxybutynin 2.5 mg/atomoxetine 75 mg (n=329) or placebo (n=331) once-daily before bedtime. According to a statement from Apnimed, the study included a demographically and clinically diverse population reflective of the real-world OSA population, with a representative distribution of gender, weight classes, and symptom severities.

• At 26 weeks, AD109-treated participants showed a mean reduction from baseline in apnea-hypopnea index (AHI) of 46.8% vs 6.8% with placebo (P<0.001).
• At week 51, the reduction in AHI seen in AD109-treated individuals remained significant (P<.001).
• At weeks 26 and 51, a significant proportion of participants treated with AD109 achieved a ≥50% reduction from baseline in AHI (P<.0001).
• For those treated with AD109, 45.0% at week 26 and 47.5% at week 51 showed improved OSA disease severity.
• 22.9% and 22.5% of those treated with AD109 at weeks 26 and 51, respectively, showed OSA complete disease control (defined as an AHI<5).
• AD109 treatment was associated with reductions in oxygen desaturation index (P<.001) and hypoxic burden (P<.0001) at weeks 26 and 51.
• No serious adverse events related to AD109 treatment were reported.

“The consistency of the promising findings across both the LunAIRo and SynAIRgy trials provides robust clinical evidence that AD109 meaningfully improved sleep apnea severity and oxygenation,” said Sanjay Patel, MD, Director of the University of Pittsburgh Medical Center’s Comprehensive Sleep Disorders Clinical Program and Study Chair for the LunAIRo clinical trial. “This is the first time we've seen a once-daily oral medication demonstrate such significant, durable effects in a broad patient population with OSA.”