If all goes well, a new drug for snoring will be approved early next year, potentially becoming the world's first landmark drug targeting the neuromuscular causes of snoring .

In July, Phase III clinical data of AD109 , a new oral drug for obstructive sleep apnea ( OSA ), was published in the American Journal of Respiratory and Critical Care Medicine . The data showed that the apnea-hypopnea index (AHI) decreased by 44.1% after treatment , and the oxygen depletion index and blood oxygen saturation were improved, indicating a significant improvement in the severity of OSA.
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AD109, developed by the US biotechnology company Apnimed , consists of the marketed drug atomoxetine and a novel isomer, R -oxybutynin , derived from the older drug oxybutynin. It works by modulating nerve signals, allowing patients to maintain airway tone during sleep and reducing the occurrence of sleep apnea. Its new drug application has been accepted by the US FDA .
" This is a promising treatment direction ," Ge Haiyan, chief physician of the Department of Respiratory and Critical Care Medicine at Huadong Hospital affiliated with Fudan University , told "Medical World." " OSA is a chronic disease that has been underestimated for a long time . Without intervention, its long-term health risks are far more serious than people imagine. "
17.6% of patients had their condition completely controlled.
OSA is caused by a decline in neuromuscular control during sleep or congenital anatomical abnormalities . Statistics show that OSA accounts for approximately 80%-90% of all sleep apnea cases , affecting nearly one billion adults worldwide.
Unlike the common understanding of "snoring," Ge Haiyan told "Medical World" that the diagnostic criteria for OSA are calculated through sleep monitoring, which measures the total number of times " breathing pauses lasting more than 10 seconds " and " blood oxygen saturation drops lasting more than 10 seconds " per hour during sleep . "These together constitute the apnea-hypopnea index (AHI) , and an AHI of 5 times per hour or more is sufficient for a diagnosis ."
She explained that currently, wearing a continuous positive airway pressure (CPAP) ventilator is the first-line treatment for moderate to severe OSA in clinical practice, which can quickly and safely open the airway and relieve symptoms of airway obstruction .
"The problem is that patients often need to wear them every night for a long time. Due to the inconvenience of carrying them when going out and the tediousness of daily cleaning and maintenance, long-term compliance has always been a prominent pain point in clinical practice, " Ge Haiyan explained.
Regarding drug treatment, to date, no oral medication has been approved for the entire OSA population that directly improves airway collapse. AD109 aims to fill this gap in clinical needs.
AD109 is an oral medication. According to the Phase III trial published in the American Journal of Respiratory and Critical Care Medicine , the study recruited 646 adult patients with mild, moderate, and severe OSA , with a median apnea-hypopnea index (AHI) of 19.6 breaths/hour . These patients had either explicitly refused to wear a ventilator or were unable to consistently wear one.
The results showed that after six months of continuous treatment, the average change in AHI in the AD109 group was -3.3 times/hour , an improvement of 44.1 % compared to before treatment . In contrast, the placebo group showed an increase of 0.7 times/hour .
Furthermore, patients in the AD109 group began to show improvement as early as the fourth week after starting medication . Six months later, their median AHI decreased from an initial 19.8 times /hour to 13.3 times/hour , and hypoxia also improved simultaneously : the nocturnal hypoxic load of patients in the AD109 group decreased by an average of 44.7%, while that in the placebo group was reduced by only 8.5%.
Ultimately, 41.8% of patients experienced a downgrade in OSA severity, with 17.6% achieving complete disease control and AHI dropping to below 5 times per hour—compared to only 9.3% in the placebo group.
" For OSA patients who are unwilling to use ventilators or do not meet the criteria for mechanical ventilation , the available treatment options are relatively limited, except for adjusting sleeping position and controlling diet. Orthodontic appliances and surgery are only suitable for certain specific groups of people," Ge Haiyan explained .
She emphasized, "However, OSA is a chronic disease , and some patients' conditions may worsen over time . Therefore , a decrease in AHI means that the condition has not only not deteriorated but has also reversed, which is a very valuable treatment outcome. "
A brand new treatment option
Ge Haiyan told "Medical World" that OSA occurs because the tension of the throat muscles decreases after the patient falls asleep, causing the upper airway to collapse or become blocked, which in turn leads to apnea .
"Sleep apnea can further lead to hypoxia, which in turn causes a drop in blood oxygen saturation, putting continuous pressure on the respiratory and circulatory systems. If not intervened in a timely and effective manner, some patients with severe OSA may develop metabolic-related diseases or even pulmonary hypertension," said Ge Haiyan.
Currently, besides ventilators, the rise of GLP-1 weight-loss drugs has provided another treatment option for obese patients with moderate to severe OSA . "However, the core logic of these drugs is still to indirectly improve the condition through weight loss . For some cases of airway muscle tone decline and airway collapse caused by aging, weight loss may not necessarily lead to a smooth recovery."
More importantly, there is a large number of non-obese OSA patients in clinical practice. Ge Haiyan's " Multidisciplinary Joint Clinic for Snoring and Sleep Medicine " at East China Hospital has observed in its clinical work that "the non-obese population is approaching 40 %".
This is another important reason why AD109 is expected to perform well .
According to the Phase III clinical trial , the enrolled patients had a BMI between 18.5 and 42 kg/m², covering almost all body types from normal to severely obese. If ultimately approved, it will theoretically be applicable to a wider range of patients, including those with mild and non-obese OSA.
Data shows that AD109 works synergistically through two drug components , acting together on the neural pathways controlling the muscles of the tongue and upper airway , enhancing nerve excitability signals , relieving inhibition of airway muscles, thereby enhancing muscle contractility, maintaining airway tension , and opening the airway .
"It acts directly on neural signaling pathways, enhancing the contractile force of airway muscles . This may be the core reason why it can benefit non-obese OSA patients to some extent, regardless of weight," said Ge Haiyan.
She analyzed, "Based on current data, this drug has indeed , and has also improved the patient's hypoxic burden . Furthermore, it is an oral medication, making treatment highly convenient and a more easily adhered -to option for patients who are resistant to or unable to consistently wear a ventilator long-term . "
However, Ge Haiyan also pointed out that, in terms of the absolute value of the reduction in AHI , even if it is successfully approved, it still cannot completely replace the ventilator. "It is more likely to be used as a combination or supplementary option for early-stage, mild OSA patients or moderate-to-severe patients . "
In fact, AD109 is not "perfect." In this study, about 21% of participants discontinued the medication due to side effects such as dry mouth, nausea, insomnia, and difficulty urinating.
In addition, many experts also believe that an average decrease of about 6-7 AHIs is "not impressive" for many severely ill patients. "The most severe patient I have seen had an AHI of more than 150. In clinical practice, many patients ' conditions are much more severe than those in the AD109 trial," commented Christopher Winter, a neurology and sleep medicine expert in the United States.
Can medication cure it completely?
Currently, AD109 data primarily reflects improvements in short-term indicators such as AHI and hypoxia index . Ge Haiyan stated that the real health threat of OSA often lies in the long-term complications arising from the disease .
" The most common systemic risk for OSA patients is the cardiovascular system , which is a cumulative process and will not appear all at once," said Ge Haiyan. This is also a major challenge in clinical research in this field —it is not difficult to see improvements in indicators in the short term, but to verify whether these improvements can be converted into long-term health benefits, more long-term follow-up evidence is often required .
Ge Haiyan further explained that , for example, long-term and repeated chronic intermittent hypoxia can lead to increased pulmonary artery pressure, which can then develop into persistent pulmonary hypertension and cor pulmonale , which is not uncommon in clinical practice . In addition, long-term hypoxia may also induce abnormal cardiac electrical activity and arrhythmia .
“ CPAP machines have been used clinically for decades , and a large amount of observational data suggests that patients who wear them regularly over a long period of time can obtain cardiovascular benefits. In contrast, AD109 is a brand-new drug, and the aforementioned long-term benefits still need time to be verified,” said Ge Haiyan .
In her view, the public's misconceptions about OSA are a more pressing issue than the limitations of current treatments .
OSA is not a disease that can be cured in a short period of time, but a chronic disease that requires long-term management . In Ge Haiyan's words, this is also the original intention of Huadong Hospital in establishing a multidisciplinary joint clinic.
" The outpatient department integrates resources from respiratory and otolaryngology departments . If a patient has obvious structural abnormalities in the throat, the otolaryngology department can assess whether surgical correction is needed. If the patient also has obesity or metabolic problems, multidisciplinary collaboration will be carried out to conduct long-term follow-up management of weight and related indicators," she explained.
Many patients wonder , "I'm not overweight, so how could I get OSA ?" Ge Haiyan explains that OSA isn't solely a matter of weight ; it's closely related to the anatomy of the upper airway . " For example, people tend to have more crowded soft tissues in the throat, making them more prone to collapse during sleep. Furthermore, as we age, the muscle tone of the airway gradually declines , and this change isn't entirely determined by weight . "
Therefore, in Ge Haiyan's view, even if AD109 is eventually approved, the overall treatment logic for OSA will not change.
" Multidisciplinary follow-up and long-term disease monitoring remain the core of managing this chronic disease . In particular, for people who snore for a long time and are suspected of having sleep apnea, they should go to the hospital as soon as possible to complete sleep monitoring and make a clear diagnosis . Standardized treatment is currently the most direct and important means to reduce the risk of long-term complications of OSA ," said Ge Haiyan.

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