Sleep apnea is a debilitating disease that many sufferers don’t even realize they have. Those afflicted with the condition will regularly stop breathing during sleep as the muscles in their throat relax, sometimes hundreds of times a night. Breathing eventually resumes when the individual’s oxygen supply gets critically low, and the body semi-wakes to restore proper respiration. The disruption to sleep causes serious fatigue and a wide range of other deleterious health effects.

Treatment for sleep apnea has traditionally involved pressurized respiration aids, mechanical devices, or invasive surgeries. However, researchers are now attempting to develop a new drug combination that could solve the problem with pharmaceuticals alone.

Breathe Into Me

There are a variety of conditions that fall under the sleep apnea umbrella, with various causes and a range of imperfect treatments. Perhaps the most visible is obstructive sleep apnea (OSA), in which the muscles in the throat relax during sleep. Under certain conditions, and depending on anatomy, this can lead the airway to become blocked, causing a cessation of breathing that requires the sufferer to wake to a certain degree to restore proper respiration. Since the 1980s, OSA has routinely been treated with the use of Continuous Positive Airway Pressure (CPAP) machines, which supply pressurized air to the face and throat to forcibly keep the airway open. These are effective, except for one major problem—a great deal of patients hate them, and compliance with treatment is remarkably poor. Some studies have shown up to 50% of patients give up on CPAP treatment within a year due to discomfort around sleeping with a pressurized air mask.

Against this backdrop, a simple pill-based treatment for sleep apnea is a remarkably attractive proposition. It would allow the treatment of the condition without the need for expensive, high-maintenance CPAP machines which a huge proportion of patients hate using in the first place. Such a treatment is now close to being a reality, under the name AD109.

The treatment aims to directly target the actual cause of obstructive sleep apnea. OSA is a neuromuscular condition, and one that only occurs during sleep—as those afflicted with the disease don’t suffer random airway blockages while awake. When sleep occurs, neurotransmitter levels like norepinephrine tend to decrease. This can can cause the upper airway muscles to excessively relax in sleep apnea sufferers, to the point that the airway blocks itself shut. AD109 tackles this issue with a combination of drugs—an antimuscarinic called aroxybutynin, and a norepinephrine reuptake inhibitor called atomoxetine. In simple terms, the aroxybutynin blocks so-called muscarinic receptors which decrease muscle tone in the upper airway. Meanwhile, the atomoxetine is believed to simultaneously improve muscle tone in the upper airway by maintaining higher activity in the hyperglossal motor neurons that control muscles in this area.

Thus far, clinical testing has been positive, suggesting the synergistic combination of drugs may be able to improve airflow for sleep apnea patients. Phase 1 and Phase 2 clinical trials have been conducted to verify the safety of the treatment, as well as its efficacy at treating the condition. Success in the trials was measured with the Apnea-Hypopnea Index (AHI), which records the number of airway disruptions an individual has per hour. AHI events were reduced by 45% in those taking AD109 when compared to the placebo group in a phase 2 trial featuring 211 participants. It achieved this while proving generally safe in early testing without causing detectable detriments to attention or memory. However, some side effects were noted with the drug—most specifically dry mouth, urinary hesitancy, and a level of insomina. The latter being particularly of note given the drug’s intention to improve sleep.

Testing on AD109 continues, with randomized Phase 3 trials measuring its performance in treating mild, moderate, and severe obstructive sleep apnea. For now, commercialization remains a ways down the road. And yet, for the first time, it appears promising that modern medicine will develop a simple drug-based treatment for a disease that leaves millions fatigued and exhausted every day. If it proves viable, expect it to become a major  pharmaceutical success story and the hottest new drug on the market.