For people forced to wear a cumbersome mask every night to avoid the potentially fatal complications of obstructive sleep apnea (OSA), the idea of simply swallowing a pill at bedtime was, until now, a fantasy. But it's within reach thanks to encouraging results from a large clinical trial released this week.
One billion people affected
Obstructive sleep apnea affects approximately one billion people worldwide. The condition is characterized by repeated breathing stops during the night—sometimes dozens or hundreds of times—causing a drop in blood oxygen levels before the patient unconsciously wakes up. Long-term risks include stroke, Alzheimer's disease, and sudden cardiac death.
The current standard of treatment relies on continuous positive airway pressure (CPAP) machines, which blow air down the throat to keep the airway open. However, these devices require the wearing of a nighttime mask, which many patients struggle to tolerate or do not use regularly.
A decade ago, scientists in Boston identified a combination of two existing drugs that could keep the upper airway open by co-stimulating the relevant muscles, including the genioglossus, a key muscle that forms most of the base of the tongue.
The first compound, atomoxetine, approved in 2002 by the US Food and Drug Administration to treat attention deficit hyperactivity disorder, increases levels of the neurotransmitter norepinephrine. In sleep apnea patients, the decrease in this substance during sleep contributes to the loss of upper airway muscle tone. The second, aroxybutynin, is a chemically modified version of a drug used for overactive bladder. It blocks certain acetylcholine receptors, preventing this neurotransmitter from inhibiting the nerve that innervates the genioglossus.
The company Apnimed, created in 2017 to commercialize this discovery, conducted a large-scale trial in 2023. The study involved 646 people suffering from OSA, randomly assigned to a group receiving the drug AD109 or a placebo group for six months. Treated participants experienced 56% fewer episodes of respiratory arrest or slowing during sleep compared to the placebo group.
Even more impressive, 22% of treated patients achieved complete disease control, defined as fewer than five obstructive episodes per hour. The company also reports that AD109 caused a significant reduction in the depth and duration of periods of low blood oxygenation, an important indicator linked to cardiovascular complications.
However, a six-month trial does not allow for the assessment of the drug's effects on long-term cardiovascular risks associated with OSA. Scientists warn of the potential side effects of atomoxetine, a stimulant that can slightly increase heart rate and diastolic blood pressure.
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