FDA Accepts NDA for AD109 for Treatment of Adults With Obstructive Sleep Apnea

The FDA accepted for review the new drug application (NDA) for aroxybutynin 2.3 mg/atomoxetine 75 mg (AD109; Apnimed, Inc) for the treatment of adults with obstructive sleep apnea (OSA), according to a news release from the manufacturer. Additionally, the FDA assigned a Prescription Drug User Fee Act target action date of February 28, 2027.¹

AD109 is an investigational agent aiming to be the first pharmacological treatment to improve oxygenation during sleep and target the neuromuscular root cause of upper airway collapse in patients with OSA. According to the manufacturer, AD109 is “a potentially first-in-class combination of aroxybutynin, a novel antimuscarinic, and atomoxetine, a selective norepinephrine reuptake inhibitor.”¹

Designed to reduce the complexity of intervention and help more people benefit from effective, restorative sleep, AD109 is a once-daily oral pill taken at bedtime. If approved, it may offer a convenient oral solution to improve oxygenation and health for people with OSA, which is especially significant in a treatment landscape marked by complex, invasive options.¹

What Clinical Trial Data Supports the NDA?

The NDA submission is supported by data from the phase 3 clinical trials SynAIRgy (NCT05813275)² and LunAIRo (NCT05811247).³ Both are randomized, double-blind, placebo-controlled trials evaluating AD109 in adults with mild, moderate, and severe OSA.¹

LunAIRo is a 51-week trial. Its primary end point is the change from baseline to week 26 in the apnea-hypopnea index with 4% desaturation (AHI4) for AD109 compared with placebo. Key secondary end points include the change from baseline in the oxygen desaturation index (ODI; 3% desaturation), the change from baseline in hypoxic burden (4% desaturation), the change from oxygen desaturation in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score, and the proportion of participants achieving a 50% or greater reduction in AHI4 at week 26.^3,4

SynAIRgy is a 26-week trial that shares the same core primary end point as LunAIRo (change from baseline to week 26 in AHI), with key secondary end points including ODI, PROMIS Fatigue T score, hypoxic burden (HB), PROMIS Sleep-Related Impairment T score, and proportion of participants with a 50% or greater reduction in AHI.^2,5

AD109 Shows Significant Reductions in AHI and Improvements in Oxygenation Metrics

LunAIRo

LunAIRo enrolled 660 participants across 64 US centers and met its primary end point of change from baseline to week 26 in AHI. Specifically, AD109-treated participants achieved a mean AHI reduction of approximately 46.8% from baseline at week 26 compared with 6.8% for placebo (P < .001). This effect remained statistically significant through the full year at week 51.⁴

Secondary and exploratory end points followed the same pattern, with meaningful reductions in HB and ODI sustained through week 51, a significant proportion of participants achieving at least a 50% AHI reduction, and improvement in OSA severity category for 45% to 48% of participants at weeks 26 and 51. Additionally, AD109 demonstrated meaningful improvements in HB and ODI index at week 26 and at the end of the study. A significant proportion of participants achieved a 50% or greater reduction in AHI, and AD109 improved OSA disease severity for 45.0% and 47.5% of participants at weeks 26 and 51, respectively.⁴

In the LunAIRo trial, AD109 was generally well tolerated, with mostly mild to moderate treatment-emergent adverse events (AEs) and no AD109-related serious AEs.⁴

SynAIRgy

The 26-week SynAIRgy trial enrolled 646 participants across 69 US and Canadian sites and achieved its primary end point. In the intent-to-treat (ITT) analysis, AD109 produced a mean AHI reduction of approximately 4 events per hour more than placebo at 26 weeks (P = .001), translating to a model-estimated 44.1% decrease from baseline vs 17.6% with placebo. In the supportive on-treatment analysis—which focused on participants who remained on active therapy—the effect was substantially larger (55.6% reduction in AHI), as later highlighted alongside the mechanistic companion publication.⁵

Beyond the primary end point, SynAIRgy showed statistically significant improvements in oxygenation. More specifically, ODI improved by 4.5 events per hour more than placebo (P = .001, ITT analysis), and HB was reduced by approximately 39.6% more than placebo (P < .0001); however, HB followed the primary in the prespecified testing hierarchy and could not be formally declared significant. The PROMIS Fatigue end point narrowly missed significance in the primary ITT analysis (P = .059) and reached significance only in the supportive on-treatment analysis (P = .030). The PROMIS Sleep-Related Impairment T score improved similarly in both arms, with no treatment effect observed between them.⁵

Regarding safety, AD109 was generally well tolerated; however, AEs led approximately 21.2% of AD109-treated patients to discontinue treatment compared with 3.1% of those receiving placebo. The most common AEs included dry mouth, insomnia, nausea, and urinary hesitation; there were no treatment-related serious AEs or deaths.⁵

“The FDA acceptance of our NDA is an important milestone for Apnimed as we advance toward our goal of expanding treatment options for people with OSA who continue to need more accessible solutions,” Kevin Lind, CEO of Apnimed, said in the news release.¹ “The NDA is supported by a clinical data package that reflects years of scientific innovation focused on a major unmet need. We believe AD109 has the potential to offer an important new treatment option for adults with OSA, if approved, and we look forward to engaging with the FDA during its review.”

REFERENCES

1. Apnimed announces FDA acceptance of new drug application for AD109, an investigational oral pill to treat adults with obstructive sleep apnea. Apnimed Inc. News release. July 14, 2026. Accessed July 20, 2026. 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/

2. Parallel-arm study to compare AD109 to placebo with patients with OSA (SynAIRgy study). ClinicalTrials.gov. Updated November 21, 2025. Accessed July 20, 2026. https://clinicaltrials.gov/study/NCT05813275

3. Parallel arm trial of AD109 and placebo with patients with OSA (LunAIRo). ClinicalTrials.gov. Updated November 21, 2025. Accessed July 20, 2026. https://clinicaltrials.gov/study/NCT05811247

4. Taranto-Montemurro L, Patel SR, Strollo PJ Jr, et al. Aroxybutynin and atomoxetine (AD109) for the treatment of obstructive sleep apnea: rationale, design and baseline characteristics of the phase 3 clinical trials. Contemp Clin Trials Commun. 2025;47:101538. doi:10.1016/j.conctc.2025.101538

5. Strollo PJ Jr, Farkas R, Taranto-Montemurro L, Cronin J, Patel SR; SynAIRgy Investigators. Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnea: a randomized phase 3 trial (SynAIRgy). Am J Respir Crit Care Med. 2026;212(7):1569-1584. doi:10.1093/ajrccm/aamag215