Editor's note: This story was updated on June 5, 2024.
May 30, 2024 – Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea.
Closure of your upper airway is the hallmark of sleep apnea. And a machine that forces air into your body through a hose and a face mask is the most common, yet expensive and obtrusive, treatment.
Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.
“In my patients, I’d say a quarter of them don’t get compliant on 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 often because they “just don’t want to wear a mask at night.”
For Kuhlmann, who's also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies you with air throughout the night.
But that may be changing.
New Pill Making Waves in Sleep Apnea
Could there be a new approach – a simple pill – that eases sleep apnea symptoms and replaces more conventional treatments?
That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea – currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.
Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.
“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”
AD109 is currently in phase III trials, but results are already out for phase II.
The conclusion of those phase II studies?
“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.
And onto phase III clinical trials the drug goes. But there’s something to consider when looking at these results.
Evaluating AD109’s Results
For phase II trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).
The index measures the average number of times someone stops breathing or has their breathing restricted per hour of sleep. Typically, a higher score means it's a more severe case.
One promising result out of the phase II trials was the lack of major side effects in people who took the drug.
“What you are kind of hoping for from a phase II trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Kirsch, who's also a former president of the American Academy of Sleep Medicine.
Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”
For those with an index score of 10 to 15 (mild), 77% had their scores lowered to below 10.
But only 42% with a score of 15 to 30 (moderate) were able to get below 10. And only 7% of those with an score of over 30 were able to get all the way down to 10 or below.
Regarding some of the index score drops, Kuhlmann said, “If you drop from an AHI of 20 to 10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”
Phase III should include a broader range of people. “Phase II provides a proof of concept … phase III is a little bit broader … you can open the use of the drug to more people,” said Kirsch.
AD109’s Impact on Oxygenation Level
With sleep apnea, your body takes in less oxygen during sleep, which causes many of its crippling effects when you’re awake.
Kirsch explained how sleep doctors look at minimum oxygen saturation when reading sleep studies, measuring how low it dropped. “Often, when you review a sleep study with a patient, you'll talk about both AHI and minimum oxygen saturation,” he said.
One thing Kuhlmann brought into question was the fact that Apnimed used something called “hypoxic burden” instead of minimum oxygen saturation levels and the time spent at those levels throughout the night.
Hypoxic burden is a relatively new data point that measures the levels of hypoxia — which is when tissues don’t get enough oxygen — caused by sleep apnea during sleep. It has emerged as an important piece of data in identifying those with high-risk sleep apnea.
Apnimed released a statement reflecting its belief that hypoxic burden is the most telling way to analyze the desaturation process throughout the night, but also provided peer-reviewed data sets that outlined several other respiratory and oxygenation parameters, most notably when blood oxygen levels dipped below 90%
In elaborating on Apnimed’s use of hypoxic burden, Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”
In its conclusion, the peer-reviewed study evaluated the efficacy of AD109 for adults with mild to severe OSA and said the drug demonstrated clinically meaningful improvement in sleep apnea.
What Therapies Must Consider for the Future
Until phase III data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.
“Like any form of data, there are going to be targeted populations that may do better … with any drug, you’re unlikely to fix everything. … Until we see that phase III data … you really can’t say for sure,” Kirsch said.
“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Kuhlmann said.
But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.
Kuhlmann said he’d like to see a medication – including AD109 – that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”
Besides AD109, Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”
Big Need for Progress
Sleep apnea is a major public health problem, and the number of people who have it rises by the year. The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea – the most common form – remain undiagnosed.
Many simply don’t know they have it. It’s their partners who often detect symptoms late at night while the other is snoring away, oblivious to their brain’s temporary, intermittent lack of oxygen.
Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway – like obesity – or causes changes in structural features that narrow the airway.
Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier … you have loss of muscle tone to your entire body, including the upper airway muscles.”
