Apnimed Submits NDA for AD109 Following Positive Phase 3 Results in Obstructive Sleep Apnea

AD109, an investigational oral therapy for obstructive sleep apnea (OSA), has been submitted by Apnimed for a New Drug Application (NDA) to the FDA. Following this submission, positive results from its phase 3 clinical development program, including the SynAIRgy (NCT05813275) and LunAIRo (NCT05811247) trials, were revealed. Collectively, these findings support the potential for AD109 to become the first oral pharmacologic treatment option for OSA, a condition traditionally managed with device-based therapies.¹

Disease Overview

Obstructive sleep apnea is a chronic sleep-related breathing disorder recognized through repeated collapse of the upper airway during sleep. This disorder commonly results in intermittent hypoxia, sleep fragmentation, and excessive daytime sleepiness. Furthermore, it has association with an increased risk of cardiovascular disease, metabolic dysfunction, and impaired quality of life.²

The traditional standard first-line therapy for moderate to severe OSA is continuous positive airway pressure (CPAP); however, long-term adherence remains a major limitation, with several patients discontinuing therapy due to experiencing discomfort, inconvenience, or intolerance. A significant unmet need for alternative treatment options, particularly pharmacologic therapies that may improve adherence and broaden access to treatment remain as a result.

AD109 is being developed as an oral, once-daily therapy that intends to reduce upper airway collapse during sleep through a pharmacologic mechanism targeting neuromuscular control of airway patency. Through modulating airway patency during sleep, it is being evaluated as a potential non-device-based treatment option for OSA. Phase 3 data were a key evidentiary component supporting the NDA submission, marking a regulatory milestone following completion of the pivotal development program.

Phase 3 Clinical Trial Program

The NDA is supported by results from the phase 3 SynAIRgy and LunAIRo trials, which evaluated the efficacy and safety of AD109 in adults with obstructive sleep apnea who were intolerant of or unwilling to use continuous positive airway pressure (CPAP) therapy.

In July 2025, Apnimed reported positive topline results from the second pivotal phase 3 LunAIRo trial, which met its primary end point of reduction in apnea-hypopnea index (AHI) at 26 weeks compared with placebo (P < .001). Participants receiving AD109 achieved a mean 46.8% reduction in AHI from baseline at week 26 versus 6.8% with placebo. The reduction in AHI remained statistically significant through week 51.³

In addition to the primary end point, AD109 demonstrated improvements across key secondary and exploratory outcomes, including oxygenation measures such as hypoxic burden and oxygen desaturation index, as well as a higher proportion of participants achieving at least a 50% reduction in AHI. Approximately 22.9% of participants achieved complete disease control, defined as an AHI of less than 5 at week 26.³

These findings were consistent with the earlier SynAIRgy phase 3 trial, which also met its primary end point and demonstrated meaningful reductions in AHI along with improvements in sleep-related breathing parameters. Across both pivotal studies, AD109 demonstrated a consistent efficacy and safety profile, providing the clinical evidence supporting Apnimed’s NDA submission to the FDA.³

Expert Perspective

Sanjay R. Patel, MD, MSc, a sleep medicine physician and researcher at Brigham and Women's Hospital and Harvard Medical School and a co-author of the phase 3 AD109 research, said the most clinically meaningful findings from the AD109 phase 3 program were the improvements observed in patient-reported symptoms, particularly daytime fatigue and snoring.

"Because the main reason we treat obstructive sleep apnea is to improve symptoms, the most meaningful findings to me are the improvement in daytime fatigue and snoring," Patel said in an interview with Pharmacy Times.

Although improvements in fatigue were modest overall compared with placebo, he noted that patients with baseline excessive daytime sleepiness experienced substantially greater benefits with AD109. He also pointed to meaningful reductions in snoring, adding that "these are two of the most common symptoms patients seek treatment for."

Patel emphasized that continuous positive airway pressure (CPAP) therapy and mandibular advancement devices (MADs) remain first-line treatment options for patients with OSA. He noted that the SynAIRgy and LunAIRo trials enrolled patients who either could not tolerate CPAP or declined its use, suggesting that AD109 may ultimately fill an important gap for patients who remain unable to use established therapies despite appropriate troubleshooting.

"For the sizable number of patients who try CPAP and MAD and cannot tolerate either, AD109 may be a viable treatment option to consider alongside tirzepatide and hypoglossal nerve stimulation," Patel said.

Patel also stated that the potential role of AD109 will likely depend on individual patient characteristics, disease severity, and the availability of other treatment options.

"Based on current information, tirzepatide may be preferred in those with moderate to severe OSA and substantial obesity, hypoglossal nerve stimulation in those with moderate to severe OSA without substantial obesity, and AD109 in those without substantial obesity who do not want surgery or those with milder severity OSA but still with substantial symptom burden," Patel noted.

Patel cautioned clinicians against focusing exclusively on reductions in apnea-hypopnea index (AHI) when evaluating emerging pharmacologic therapies.

"Although the AHI plays a central role in defining who has OSA, this metric has never been validated as a therapeutic biomarker," he said. "As a result, it is much more important to know how various treatments address clinically meaningful endpoints like symptoms rather than focus solely on the change in AHI."

Patel also emphasized the importance of evaluating outcomes beyond traditional sleep metrics and carefully matching therapies to appropriate patients. "I think it is very important to assess which symptoms are improved with emerging pharmacologic therapies as well as which patients would be poor candidates for a particular treatment due to the side effect profile," Patel said.

Clinical Significance and Timing of Submission

The timing of the NDA submission follows the accumulation of pivotal phase 3 evidence in 2025, which established a reproducible treatment effect across 2 large clinical trials. This regulatory milestone is a reflection of both the unmet clinical need in obstructive sleep apnea and growing interest in oral therapeutic approaches that may improve long-term adherence compared with existing therapies.

If approved, AD109 could represent a meaningful shift in the treatment paradigm for OSA by introducing a pharmacologic option in a field historically dominated by mechanical airway support.

REFERENCES

1. Apnimed Announces Publication of its Phase 3 SynAIRgy Trial of AD109 for Obstructive Sleep Apnea in the American Journal of Respiratory and Critical Care Medicine. Apnimed. News release. May 2026. Accessed June 3, 2026. https://apnimed.com/article/apnimed-dual-publication-press-release/

2. Jordan, A. S., McSharry, D. G., & Malhotra, A. (2014). Adult obstructive sleep apnoea. Lancet (London, England), 383(9918), 736–747. https://doi.org/10.1016/S0140-6736(13)60734-5

3. Apnimed reports positive topline results from second phase 3 trial of AD109, reinforcing potential of first oral pill for obstructive sleep apnea. Apnimed. News release. July 23, 2025. Accessed June 3, 2026. https://apnimed.com/article/ad109toplinephase3results/