Anyone who suffers from obstructive sleep apnea has had to wear a breathing mask night after night. The treatment is effective but uncomfortable and unpopular. But there could soon be an alternative: a tablet to be taken before sleep is supposed to stimulate the muscles in the throat and prevent the airways from collapsing during sleep. In a phase 3 clinical trial, the drug, called AD109, reduced the number of nocturnal pauses in breathing and improved oxygen delivery. The manufacturer has now applied for approval in the USA.
In sleep apnea, the tongue and throat muscles relax during sleep, causing the airways to temporarily collapse and pauses in breathing. This causes the oxygen saturation in the blood to drop and the body switches to alarm mode. The heartbeat accelerates and those affected often wake up, so their sleep is less restful. The risk of cardiovascular disease and other health problems also increases. To date, the gold standard therapy is continuous positive pressure ventilation (CPAP). To do this, those affected must wear a breathing mask night after night that keeps the airways open with slight excess pressure. Although this therapy helps when used correctly, many patients find the mask annoying and impractical and report problems when using it. The low level of acceptance means that many of those affected have not yet received suitable therapy.
Less pauses in breathing
But a new medication could soon provide relief: a tablet taken daily before going to sleep is said to stabilize the respiratory muscles and thus keep the airways open. As a team led by Patrick Strollo from the University of Pittsburgh reports, the drug called AD109 led to a significant reduction in pauses in breathing and improved oxygen supply in a phase 3 clinical trial. The results are consistent with those from previous clinical studies.
The study involved 646 people at 69 centers in the United States and Canada who could not tolerate or refused CPAP treatment. The severity of sleep apnea varied among the participants from mild forms with five to 15 nocturnal pauses in breathing per hour to severe forms with more than 30 pauses in breathing per hour. After a treatment period of 26 weeks, the people who received AD109 experienced an average of 3.3 fewer pauses in breathing per hour, and 0.7 more pauses in the placebo group. For around 40 percent of those treated, the number of pauses in their breathing at night was halved and 22.3 percent even had less than five pauses in breathing per hour, which corresponds to the normal value without sleep apnea.
Combined effect
Other measurements also improved: oxygen saturation in the blood increased and hypoxic stress decreased. This applied to people of normal weight as well as to people who were overweight or obese. The side effects were mostly mild. The test subjects most commonly reported dry mouth, nausea, insomnia and difficulty urinating. Around 21 percent of volunteers in the treatment group and three percent in the placebo group discontinued therapy due to side effects. There were no plans to reduce the dose as part of the study. In clinical practice, however, it would be possible to adjust the dose individually and in this way possibly reduce side effects, as the team explains.
“The results provide encouraging evidence that targeting neuromuscular dysfunction can lead to meaningful clinical outcomes, consistent with our evolving understanding of disease biology,” says Strollo. The drug AD109 combines two active ingredients: aroxybutynin, which blocks the effects of the neurotransmitter acetylcholine, and the selective norepinephrine reuptake inhibitor atomoxetine, which is used, among other things, to treat ADHD. Together, both active ingredients ensure that muscle tension in the upper airways does not drop too much during sleep.
Approval applied for
From Strollo and his colleagues’ perspective, the anti-apnea pill could offer an easy-to-use alternative for people with sleep apnea who cannot cope with the CPAP sleep mask and therefore remain untreated. “A tablet that targets the underlying neuromuscular causes of airway collapse during sleep could help close this gap and expand the range of effective options for patients,” says Strollo.
In the USA, the manufacturer Apnimed has now applied for approval for AD109. If the US Food and Drug Administration (FDA) grants approval, the drug could come onto the market in the US as early as early 2027. It is still unclear whether and when AD109 will also be approved in Europe.
Source: Patrick Strollo (University of Pittsburgh, Pennsylvania, USA), American Journal of Respiratory and Critical Care Medicine, doi: 10.1093/ajrccm/aamag215