Results from the SynAIRgy trial show the investigational oral therapy AD109 significantly reduced airway obstruction and improved oxygenation in patients with obstructive sleep apnea.

Key takeaways:

• The phase 3 SynAIRgy trial met its primary endpoint, showing a 55.6% reduction in the apnea-hypopnea index for patients taking AD109 compared to placebo.
• AD109, a combination of aroxybutynin and atomoxetine, targets the underlying neuromuscular causes of airway collapse in patients who cannot tolerate or refuse CPAP therapy.
• Apnimed has submitted a New Drug Application to the FDA, with a potential PDUFA target action date expected in the first quarter of 2027.

Apnimed Inc announced the simultaneous publication of two peer-reviewed articles on AD109 (aroxybutynin 2.5 mg/atomoxetine 75 mg), an investigational, once-daily oral pill taken at bedtime designed to improve oxygenation and target the neuromuscular root cause of obstructive sleep apnea (OSA).

The phase 3 SynAIRgy trial results are published in the American Journal of Respiratory and Critical Care Medicine, alongside a companion mechanistic review article in the American Journal of Respiratory Cell and Molecular Biology that highlights AD109’s neuromuscular mechanism of action.

The SynAIRgy trial was a randomized, double-blind, placebo-controlled six-month clinical trial enrolling 646 adult participants with mild to severe OSA who failed or refused CPAP.

“The publication of the SynAIRgy phase 3 results, together with a companion review article on the underlying biology, provides important insights into OSA as a treatable, multifactorial disease,” says Patrick J Strollo Jr, MD, study chair of the SynAIRgy clinical trial and vice chair of medicine for Veterans Affairs at the University Pittsburgh School of Medicine, in a release. “These data support neuromuscular dysfunction as a key driver of disease and demonstrate that targeting this pathway can lead to meaningful improvements in objective physiologic measures, including airway obstruction and oxygenation.”

Results from the SynAIRgy trial, as published in the American Journal of Respiratory and Critical Care Medicine, include:

• Primary endpoint met: 55.6% reduction in apnea-hypopnea index (AHI) (≥ 4% desaturation criterion for hypopneas) from baseline to week 26 (p≤0.0001 vs placebo)
• Significant improvements in oxygenation: 60.5% reduction in geometric mean in hypoxic burden (p<0.0001 vs placebo) from baseline to week 26; mean reduction of 6.5 events/hr in oxygen desaturation index (p<0.0001 vs placebo) from baseline to week 26
• Significant response rates: 39.6% of participants had AHI reductions ≥ 50% (p<0.0001 vs placebo); 22.3% of participants achieved disease control (AHI <5 events/hour)
• Broad and consistent clinical outcomes: Observed across participants with mild, moderate, and severe OSA; consistent in participants with and without obesity
• Early signals of clinical activity and sustained results: Improvements observed as early as week 4 and maintained through week 26.

AD109 was generally well-tolerated. The most common adverse events were dry mouth, insomnia, nausea, and difficulty urinating, which were consistent with earlier AD109 clinical trials. Around 21% of patients discontinued therapy due to side effects, and no serious adverse events related to AD109 were reported.

“OSA is a complex and heterogeneous disease. A one-size-fits-all approach has left many people with OSA without a treatment that works for them,” says Neomi Shah, MD, MPH, MSc, ATSF, chair of the sleep and respiratory neurobiology assembly at the American Thoracic Society, in a release. “Advances that connect clinical outcomes with underlying biology and explore new therapeutic approaches are essential to moving toward more personalized care. The SynAIRgy study helps move the field closer to that goal.”

AD109 combines two medications, aroxybutynin and atomoxetine, which work together to support muscles in the throat and prevent the airway from sagging or collapsing during sleep.

“In many other chronic diseases, such as cardiovascular disease, asthma, or type 2 diabetes, it would be unthinkable for the majority of diagnosed patients to remain untreated or undertreated. Yet that remains the reality in OSA,” says Strollo, in a release. “An oral pill that targets the underlying neuromuscular drivers of airway collapse during sleep could help address this gap and broaden the range of effective options for patients who remain untreated today.”

AD109 has received Fast Track designation from the US Food and Drug Administration (FDA) for the treatment of OSA.

“Peer-reviewed publication of our phase 3 data, alongside a mechanistic review article, represents an important milestone in establishing a scientific foundation for AD109,” says Larry Miller, MD, CEO of Apnimed, in a release. “We believe these publications reinforce the strength of our clinical data and the potential for AD109 to address a significant unmet need in OSA, where many people with OSA remain untreated or inadequately treated. As we advance toward potential commercialization, we are focused on delivering a differentiated, convenient oral therapy that may expand treatment access and improve patient outcomes.”

Apnimed has submitted its New Drug Application (NDA) for AD109 to the FDA. Based on the FDA’s prior feedback, Apnimed expects a potential Prescription Drug User Fee Act (PDUFA) target action date in the first quarter of 2027, subject to FDA acceptance of the NDA for review.

More on Apnimed:

ID 406149814© Chel| Dreamstime.com