Editor's note: This story was updated on June 5, 2024.
May 30, 2024 – About 30 to 40 million people within the United States and nearly a billion people worldwide have Sleep apnea.
The closure of the upper airway is the hallmark of sleep apnea. The commonest, but additionally most costly and intrusive, treatment is a machine that forces air into your body through a tube and face mask.
Because they’re cumbersome and infrequently uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure devices (CPAP) machine.
“I would say a quarter of my patients are non-compliant with the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, Mo. That's actually because they “just don't want to wear a mask at night.”
Kuhlmann, who can also be a spokesperson for the American Academy of Sleep Medicine, believes that no other treatment can replace continuous ventilation throughout the night.
But that would change.
New pill causes a stir in sleep apnea
Could there be a brand new approach – an easy pill – that would relieve the symptoms of sleep apnea and replace more conventional treatments?
That is what researchers at Apnimed hope. Apnimed is an organization that has developed a brand new oral drug for sleep apnea – currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.
Aroxybutynin is used to treat the symptoms of overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.
“The drug is unique in that there is currently no approved drug to treat sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 works by preventing the airway from collapsing at night. And it accomplishes that function through a combination of drugs that theoretically help keep the airway a little more open, but also help keep people sleeping.”
AD109 is currently in Phase III trials, but Phase II results are already available.
The conclusion of those Phase II studies?
“AD109 demonstrated a clinically meaningful improvement in [sleep apnea]which suggests that further development of the compound is justified.” This comes directly from the published data from the study.
And the drug is entering Phase III clinical trials. When these results, nevertheless, there’s something to think about.
Evaluation of the outcomes of AD109
For the Phase II trials, patients were divided into groups based on the severity of their sleep apnea using the apnea-hypopnea index (AHI).
The index measures the common variety of pauses in respiration or respiration difficulties per hour of sleep. The next value often means a more severe case.
A promising results of the Phase II trials was the absence of significant unwanted side effects in those taking the drug.
“What you hope to see from a Phase II trial, both from a safety and efficacy perspective, is that there is actually a change in the severity of sleep apnea compared to placebo,” said Kirsch, who can also be past president of the American Academy of Sleep Medicine.
According to Kuhlmann, they noticed two essential things: The apnea-hypopnea index decreased in patients who received two different doses of the drug. Patients within the lower dose group even experienced a “clinically significant improvement in fatigue.”
For 77% of those with an index value of 10 to fifteen (mild), the worth fell to below 10.
But only 42% with a rating of 15 to 30 (moderate) managed to get below 10. And only 7% of those with a rating above 30 managed to get all of the strategy to 10 or below.
Regarding a number of the index value drops, Kuhlmann said: “If you go from an AHI of 20 to 10, that is still OSA [obstructive sleep apnea] if you suffer from diabetes, high blood pressure, depression, daytime fatigue or insomnia.”
Phase III should include a wider range of individuals. “Phase II provides a proof of concept… Phase III is a little broader… you can open up the use of the drug to more people,” Kirsch said.
Effects of AD109 on oxygen levels
With sleep apnea, your body takes in less oxygen when you sleep, which causes most of the impairing effects if you are awake.
Kirsch explained how sleep medicine specialists have a look at minimum oxygen saturation when evaluating sleep studies and measure how low it drops. “When you go through a sleep study with a patient, you often talk about both AHI and minimum oxygen saturation,” he said.
Among other things, Kuhlmann questioned the proven fact that Apnimed used a so-called “hypoxic load” as a substitute of minimum oxygen saturation levels and the time spent at that level overnight.
Hypoxic stress is a comparatively latest data point that measures the degree of hypoxia—when tissues don’t get enough oxygen—attributable to sleep apnea during sleep. It has emerged as a crucial data piece in identifying people at high risk for sleep apnea.
Apnimed issued a press release expressing its belief that hypoxic stress is probably the most informative strategy to analyze the desaturation process in the course of the night, but additionally stated Peer-reviewed data sets that outlined several other respiratory and oxygen parametersespecially when the oxygen content within the blood falls below 90%
Explaining Apnimed's use of hypoxic stress, Kirsch said, “If 99% of a sleep study was at 90% and above, but there was a dip at 80%, that's not the same as spending 45 minutes below 88%. What you really want to talk about is how severe or how long does that oxygen deprivation last?”
In its conclusion, the peer-reviewed study evaluated the effectiveness of AD109 in adults with mild to severe OSA and located that the drug showed clinically meaningful improvement in sleep apnea.
What therapies must take note of in the longer term
Until Phase III data can be found, it can’t be said with certainty whether AD109 alone can work in individuals with various degrees of severity.
“As with any type of data, there will be certain target groups that may do better… No drug can cure everything. … Until we see the Phase III data… we really can't say for sure,” Kirsch said.
“It appears that AD109 treats a milder spectrum rather than perhaps the patients who would benefit most from it,” Kuhlmann said.
However, he said AD109 could still work well for many individuals. It's just essential to know that a pill can’t be in comparison with positive airway pressure.
Kuhlmann said he would really like to see a drug – including AD109 – that would compete equally well with oral devices or other agents used to treat mild to moderate cases and “that has some clinical scales associated with it that are positive.”
In addition to AD109, Kirsch said, “I believe we may be on the verge of having some drugs in the coming years that could help with sleep apnea.”
Great need for progress
Sleep apnea is a significant public health problem and the number of individuals affected increases yearly. The American Academy of Sleep Medicine estimates that as much as 80% of individuals with obstructive sleep apnea – probably the most common form – are undiagnosed.
Many simply don't know they’re affected by it. It is their partners who notice the symptoms, often late at night, while the opposite snores and doesn't notice the temporary, intermittent lack of oxygen to their brain.
Cigarette smoking, heavy alcohol consumption, drugs or neurological disorders are common risk aspects, but most significantly, anything that reduces muscle tone across the upper airway – corresponding to obesity – or causes structural changes that narrow the airways.
Kuhlmann stressed the importance of weight issues in relation to sleep apnea. “It's a very common condition, especially as people get older and heavier… muscle tone throughout the body decreases, including in the upper respiratory tract.”