SCOFA Article

Overview

Nearly one billion people worldwide may have obstructive sleep apnea (OSA), yet many remain undiagnosed or inadequately treated.^[1]

For many years, treatment has largely revolved around mechanical solutions, such as continuous positive airway pressure (CPAP).

AD109 has completed two large Phase 3 trials with positive results.^[8,10]The FDA has accepted its New Drug Application for review and assigned a PDUFA target date of February 28, 2027.^[9]

Acceptance of the application means the FDA has agreed to review it; the medication has not yet been approved.

The new medication doesn't physically keep the airway open; instead, it addresses the biological problem that causes the airway to close in the first place.

With strong Phase 2 and Phase 3 data now in hand, this treatment could represent a meaningful shift in how OSA is managed for patients who cannot or will not use CPAP.

This article breaks down the science, the trials, and what this could mean for patients and clinicians alike.

Understanding Obstructive Sleep Apnea and Its Treatment

OSA is a long-term condition in which the airway collapses repeatedly during sleep, making breathing difficult.^[2]

These breaks, called apneas (complete pauses) or hypopneas (partial reductions), can occur dozens or even hundreds of times a night.

The effects of OSA go beyond snoring and poor sleep. It has been associated with multiple chronic health conditions and an increased risk of death.^[3,4]

At its core, OSA is caused by a mix of anatomical and neuromuscular factors. During sleep, the muscles that help keep the airway open, especially those in the throat, naturally relax. In people with OSA, the airway becomes too narrow or closes completely.

The gold standard treatment for OSA is continuous positive airway pressure (CPAP).^[5] It works by sending pressured air through a mask to keep the airway open.

In principle, CPAP works quite well. In practice, adherence is a major problem because many patients struggle with it. Many patients either refuse CPAP outright or stop using it over time, leaving a big gap in treatment that medicines might be able to address.

While medications are a part of managing OSA, available ones don’t actually treat the condition itself. Instead, they focus on symptoms, especially daytime sleepiness. AD109 is different in that way.

What Is AD109?

AD109 combines two agents: atomoxetine and aroxybutynin, with complementary effects and mechanisms of action.^[6]

Atomoxetine increases nerve signaling that activates the upper-airway muscles, while aroxybutynin limits signals that allow those muscles to relax too much during sleep. Together, they are designed to help prevent the airway from narrowing or collapsing.^[6]

Clinical Trials: What Studies Have Shown So Far

Before advancing to large-scale Phase 3 trials, AD109 underwent earlier studies to determine whether this dual-mechanism approach could provide meaningful clinical benefits.^[6]

In preliminary crossover trials involving people with mild-to-moderate OSA, a single-night treatment with AD109 produced dose-dependent reductions in the apnea-hypopnea index (AHI), suggesting an immediate improvement in airway stability.^[6]

The Phase 2 MARIPOSA trial included 211 people with an AHI of 10 to 45 events per hour. It was a randomized, placebo-controlled study.^[7]

Over one month, AD109 reduced AHI by an average of 47.1% compared with placebo.^[7] About 25% of participants experienced reductions of more than 70%, while about 10% experienced reductions of more than 90%.^[7]

Participants also experienced a statistically significant reduction in fatigue, as measured by PROMIS-Fatigue scores.^[7] These findings supported the clinical potential of targeting neuromuscular control in OSA.

Phase 3 Results: Confirmed Efficacy at Scale

Researchers tested AD109 in two large Phase 3 trials involving more than 1,300 adults with mild-to-severe obstructive sleep apnea who were unable or unwilling to use positive airway pressure therapy.^[6,8]

Participants took AD109 once each night. The studies were randomized, double-blind, and placebo controlled, meaning participants were assigned to receive either AD109 or a placebo, and neither they nor the researchers knew which treatment they received during the trial.^[6,8]

In the SynAIRgy trial, AD109 reduced the apnea-hypopnea index, or AHI, by an estimated 44.1% after 26 weeks compared with placebo. AHI measures how many times breathing stops or becomes significantly reduced during each hour of sleep. Among participants who remained on treatment, the estimated reduction reached 55.6%.^[8]

In the LunAIRo trial, manufacturer-reported topline results showed a 46.8% reduction in AHI after 26 weeks compared with placebo. The treatment effect remained statistically significant through Week 51.^[10]

A pooled analysis of both trials also found that AD109 improved oxygen-related measures during sleep, including hypoxic burden, which reflects the overall severity and duration of oxygen drops.^[11]

The most common treatment-emergent side effects included dry mouth, insomnia, nausea, difficulty urinating, sleepiness, and constipation.^[11]

A pooled analysis of SynAIRgy and LunAIRo found that AD109 improved oxygenation, including a greater reduction in hypoxic burden than placebo.^[11]

Across the pooled Phase 3 analysis, the most common treatment-emergent side effects were dry mouth, insomnia, nausea, urinary hesitation, somnolence, and constipation.^[11]

A Broader Definition of Success

While the primary outcome remains the change in AHI after 26 weeks, the trials deliberately take a more holistic view of treatment success.

Beyond counting breathing disruptions, researchers also evaluated oxygenation and patient-reported outcomes. PROMIS measures and the Epworth Sleepiness Scale were used to assess fatigue, sleep impairment, and daytime sleepiness, providing a broader picture of how treatment affected participants.^[7,11]

The Takeaway: Why the AD109 Trials Matter

When considering the scale of OSA, the limitations of CPAP, the mechanism of AD109, the positive Phase 2 and Phase 3 results, and the FDA’s acceptance of the NDA, AD109 represents an important step toward expanding treatment options for people who cannot tolerate or do not wish to use positive airway pressure therapy.

If approved, AD109 could deliver a simpler, once-nightly oral option for the millions of people who currently struggle with or avoid existing therapies.

References

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Taranto-Montemurro, L., Patel, S. R., Strollo, P. J., Jr., Cronin, J., Yee, J., Pho, H., Werner, A., & Farkas, R. (2025). Aroxybutynin and atomoxetine (AD109) for the treatment of obstructive sleep apnea: Rationale, design and baseline characteristics of the phase 3 clinical trials. Contemporary Clinical Trials Communications, 47, Article 101538. https://doi.org/10.1016/j.conctc.2025.101538
Schweitzer, P. K., Taranto-Montemurro, L., Ojile, J. M., Thein, S. G., Drake, C. L., Rosenberg, R., et al. (2023). The combination of aroxybutynin and atomoxetine in the treatment of obstructive sleep apnea (MARIPOSA): A randomized controlled trial. American Journal of Respiratory and Critical Care Medicine, 208(12), 1316–1327. https://doi.org/10.1164/rccm.202306-1036OC
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Apnimed, Inc. (2026, July 14). Apnimed announces FDA acceptance of New Drug Application for AD109, an investigational oral pill to treat adults with obstructive sleep apnea. https://apnimed.com/article/apnimed-announces-fda-acceptance-of-new-drug-application-for-ad109-an-investigational-oral-pill-to-treat-adults-with-obstructive-sleep-apnea/
Apnimed, Inc. (2025, July 23). Apnimed reports positive topline results from second pivotal Phase 3 trial of AD109 in obstructive sleep apnea. https://apnimed.com/article/ad109toplinephase3results/
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Oral Medication for Sleep Apnea Completes Phase 3 Trials