Efficacy of Apnimed's Novel Oral Formulation Targeting OSA Confirmed in Second Phase 3 Trial

Apnimed’s investigational oral treatment for obstructive sleep apnea (OSA), AD109 (aroxybutynin 2.5 mg/atomoxetine 75 mg), met its primary endpoint in a second phase 3 trial, LunAIRo, significantly reducing airway obstruction and reinforcing earlier findings from the SynAIRgy trial,2 according to a July 23 announcement from the company.1

At 26 weeks, study participants receiving AD109 achieved a mean 46.8% reduction in Apnea-Hypopnea Index (AHI) from baseline, compared to 6.8% for those receiving placebo (P <.001). The improvement persisted through week 51 (P <.001), with no serious adverse events attributed to the drug, Apnimed reported.1

AD109 as a first-in-class, oral anti-apneic neuromuscular modulator that addresses the root cause of OSA by increasing upper airway muscle tone during sleep, Apnimed explained. The once-daily oral formulation combines a novel antimuscarinic (aroxybutynin) with a norepinephrine reuptake inhibitor (atomoxetine) and is in development for individuals with OSA who are intolerant of or decline continuous positive airway pressure (PAP) therapy.1

Diverse Study Population

The 12-month LunAIRo study enrolled 660 adults across 64 US centers, representing a broad range of disease severity, weight classes, and demographic backgrounds to reflect the real-world OSA population. The final cohort for analysis was approximately half (46%) women and was distributed across mild (37%), moderate (33%), and severe (30%) OSA. The participants were randomly assigned to receive either AD109 or placebo once nightly.

“With two large phase 3 studies now demonstrating a consistent and significant efficacy profile for AD109, we are closer to delivering the first oral pharmacotherapy for over 80 million US adults with OSA,” Larry Miller, MD, Apnimed chief executive officer, said in the statement. “Given the scale of unmet need in OSA, where the majority of patients remain untreated, we believe AD109, as a simple once-daily oral drug, has the potential to expand and reshape the treatment landscape."

In addition to the primary outcome, AD109 showed statistically significant improvements in secondary and exploratory endpoints:

• Reductions in hypoxic burden (P <.001) and oxygen desaturation index (P <.001)
• A higher proportion of participants achieving a a reduction in AHI of 50% or greater at weeks 26 and 51 (P <.001 for both time points)
• Improvement in disease severity in 45.0% of participants at week 26 and in 47.5% at week 51
• AHI scores consistent with complete disease control (AHI less than 5) were achieved in 22.9% at week 26 and 22.5% at week 51

“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,” Sanjay Patel, MD, study chair for the LunAIRo trial and Director of the UPMC Comprehensive Sleep Disorders Clinical Program. “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.”

Estimates suggest that 25% to 30% of men and 9% to 17% of women in the US meet the criteria for OSA. Prevalence of the disorder is known to increase with age and OSA disparately affects Hispanic, Black, and Asian populations.3 The increasing number of US adults affected by OSA is thought to be a consequence of rising obesity rates, but additional risk factors include use of alcohol and smoking. Anatomical factors also play a role in etiology (eg, facial elongation, adenoid and tonsillar hypertrophy).3

Patient advocate Emma Cooksey, Sleep Apnea Program Manager at Project Sleep, said the results offer encouragement for individuals living with OSA, including herself. “The vast number of people currently living with untreated OSA points to a need for additional treatment options. As someone living with OSA, the LunAIRo study gives me hope that novel pharmacotherapy treatments are on the horizon and can potentially improve so many lives. Innovation in this space is long overdue, and it’s encouraging to see meaningful progress being made.”1

Based on the phase 3 data from the LunAIRo and SynAIRgy trials, Apnimed plans to file a New Drug Application (NDA) with the FDA in early 2026. Additional analyses from both studies are ongoing and will be presented at a future medical congress, according to the statement.

References

1. Apnimed reports positive topline results from second Phase 3 trial of AD109, reinforcing potential of first oral pill for obstructive sleep apnea. News release. Apnimed. July 23, 2025. Accessed July 23, 2025. https://apnimed.com/article/ad109toplinephase3results/

2. Halsey G. Investigational oral medication for OSA meets primary endpoints in phase 3 clinical trial. Patient Care. May 20, 2025. https://www.patientcareonline.com/view/investigational-oral-medication-for-osa-meets-primary-endpoints-in-phase-3-clinical-trial

3. Slowick JM, Sankari A, Collen JF. Obstructive sleep apnea. StatPearls. Updated March 4, 2025. Accessed July 23, 2025. https://www.ncbi.nlm.nih.gov/books/NBK459252/