Positive Topline Results From Phase 3 Trial of AD109, First Oral Pill for Obstructive Sleep Apnea

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Apnimed today announced positive topline results from the LunAIRo study, its second pivotal phase 3 clinical trial of their lead candidate, AD109 (aroxybutynin 2.5 mg/atomoxetine 75 mg) for obstructive sleep apnea (OSA).

AD109 is a first-in-class, anti-apneic neuromuscular modulator that targets the root cause of OSA by increasing upper airway muscle tone during sleep. It is designed to be a once-daily pill taken at bedtime.

“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,” said Larry Miller, MD, chief executive officer of Apnimed.¹

The LunAIRo study is a 12-month randomized, double blind, placebo-controlled, parallel-arm, 1-year clinical trial of AD109, with an investigational fixed dose combination of aroxybutynin 2.5 mg/atomoxetine 75 mg, in participants with OSA who cannot tolerate or currently refuse continuous positive airway pressure therapy. Investigators enrolled a diverse range of 660 adult participants from 64 centers in the US, who were randomly assigned 1:1 to either AD109 or placebo (AD109, n=329; placebo, n=331) and instructed to take their assigned treatment once-daily before bedtime. Participants included 46% females, multiple racial groups, and varied weight classes. Additionally, the participants represented a range of OSA severity, including mild (37%), moderate (33%), and severe (30%) levels.

LunAIRo met its primary endpoint, demonstrating clinically meaningful and statistically significant reductions in airway obstruction at 26 weeks. Participants treated with AD109 achieved a mean reduction in the Apnea-Hypopnea Index (AHI) of 46.8% from baseline at week 26 (vs 6.8% with placebo; P<0.001). The reduction in AHI remained significant at end of study (week 51, P<0.001).

As to safety profile, AD109 was generally well-tolerated, with the most common treatment-emergent adverse events being mild or moderate in severity, and consistent with prior studies. No serious adverse events related to AD109 were reported.

The LunAIRo topline results are consistent with the previous positive topline results from the SynAIRgy phase 3 clinical trial, which was a randomized, double blind, placebo-controlled, parallel-arm 6-month clinical trial of AD109 in participants with OSA who cannot tolerate or currently refuse continuous positive airway pressure therapy. The trial enrolled 646 adult participants who were randomly assigned 1:1 to either AD109 or placebo. It met its primary endpoint of mean change from baseline in the AHI at 26 weeks compared with placebo (P=0.001).²

“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, study chair for the LunAIRo clinical trial and director of the UPMC Comprehensive Sleep Disorders Clinical Program in Pittsburgh, Pennsylvania. “This is the first time we have seen a once-daily oral medication demonstrate such significant, durable effects in a broad patient population with OSA.”¹

Investigators are still analyzing additional objective, subjective, and exploratory endpoints and safety data from the LunAIRo and SynAIRgy studies, and are anticipated to report this analysis at a medical congress later this year.

“With 2 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,” said Miller. “Based on the phase 3 data from LunAIRo and SynAIRgy, Apnimed plans to file a New Drug Application (NDA) with the US FDA in early 2026. As we prepare for FDA regulatory filing and commercialization of AD109, we are focused on ensuring we have the capabilities, people, and partnerships in place to bring this innovative drug to patients suffering from OSA and the clinicians who treat them.”¹

AD109 also demonstrated improvements in additional topline secondary and exploratory endpoints in the LunAIRo study, such as meaningful improvements in oxygenation as assessed by reductions in hypoxic burden (P<0.0001) and oxygen desaturation index (P<0.001) at week 26 and at end of study (week 51). A significant proportion of participants also achieved a ≥50% reduction in AHI from baseline at week 26 (P<0.0001) and at week 51 (P<0.0001). Notably, AD109 improved OSA disease severity for 45.0% of participants at week 26 and 47.5% at week 51; and AD109 achieved OSA complete disease control (AHI<5) for 22.9% of participants at week 26 and 22.5% at week 51.

“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,” said Emma Cooksey, a patient advocate and sleep apnea program manager at Project Sleep. “Innovation in this space is long overdue, and it is encouraging to see meaningful progress being made.”¹

“We’re especially grateful to the study participants, the investigators, and the study sites that contributed to our AD109 phase 3 clinical program. Their partnership and trust have been instrumental in advancing a new approach to OSA—one that has the possibility of changing how this chronic disease is treated,” concluded Miller.¹

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. July 23, 2025. Accessed July 23, 2025. https://apnimed.com/article/ad109toplinephase3results/

2. Apnimed announces positive topline results in the first landmark phase 3 clinical trial of AD109, an investigational once-daily oral pill for obstructive sleep apnea. News release. May 19, 2025. Accessed July 23, 2025. https://apnimed.com/article/ad109phase3toplineresults/