5 min readThere’s a lot of hype around medications lately, and with good reason. You can take a pill to lose a significant amount of weight, lower your cholesterol, and so much more, allowing for impressive medical advances in the fight against chronic conditions. Unfortunately, that sometimes means things get blown out of proportion.
Case in point: Apimed’s AD109. This is an experimental medication that’s getting a ton of early buzz. If it’s approved by the Food and Drug Administration (FDA), it would be the first oral pill for sleep apnea.
Clinical trial results for this medication are promising. As a result, AD109 has been called the “holy grail" treatment for sleep apnea, and a sleep apnea “star,” among other things. But some sleep medicine doctors say the findings are being overblown—and that the medication still won’t revolutionize treatment in people with severe sleep apnea.
MH neurologist and sleep advisor W. Christopher Winter, MD, says he’s “very frustrated” at the coverage surrounding this medication. “It creates confusion for my patients, unrealistic expectations, and flat-out seems to lie at times. That translates into more time I have to spend with individuals undoing what is being done to drum up interest in and potential users of this new drug—which is still a long way off,” he says.
That doesn’t mean there isn’t potential value in this experimental medication, per Winter—it’s just not exactly as it’s being portrayed. People imagine it's going to take the place of a CPAP or otherwise change everything and help them get the kind of rest they want. It might be helpful, but might not be as revolutionary as people want it to be. Here’s why.
What does the data suggest about Apimed’s AD109?
“In many people with obstructive sleep apnea, the muscles that keep the airway open relax too much during sleep, leading to airway collapse, disrupted breathing, and drops in oxygen levels,” says John Cronin, MD, chief medical officer for Apnimed. AD109 aims to address these issues.
The drug is a combination of medications: aroxybutynin and atomoxetine (Strattera). Aroxybutynin is a drug that can alter tongue muscle tone during sleep (it's a chemical cousin of a drug—oxybutynin—that already exists), explains Kelly Johnson-Arbor, MD, a toxicologist at MedStar Health. “Atomoxetine is a medication that enhances chemical transmission of norepinephrine in the brain,” she says, an action that boosts muscle tone in the airwway while sleeping. In combination, these drugs "appear to promote airway opening and tongue function during sleep, which may lead to improvement in the signs and symptoms of sleep apnea for some people," she adds.
The pill is designed to be taken once a night with the goal of reducing those breathing interruptions and improving oxygen intake, Cronin explains. “More broadly, the goal is to expand treatment options for people with obstructive sleep apnea, particularly those who struggle with existing therapies,” he says.
Clinical trial results have been promising so far. The latest phase 3 clinical trial results published in July found that in people with obstructive sleep apnea, the medication improved disease severity for 45 percent of people by week 26 and 47.5 percent of them by week 51.
The study also looked at the apnea-hypopnea index, a measurement of the average number of breathing disruptions that happen per hour of sleep. They saw that in people who took AD109, there was a mean reduction in the number of disruptions of 46.8 percent by week 26. Those who took a placebo saw a 6.8 percent drop. Also by week 26, a little more than 1 in 5 participants (22.9 percent) on AD109 found complete control of their sleep apnea. The medication was also well-tolerated.
That all sounds great—and it is. But there’s an important caveat.
The hype surrounding AD109 really took off after the release of results from its phase 2 clinical trial, dubbed the MARIPOSA study.
“The average patient in the MARIPOSA study had an average of 19.55 breathing problems per hour. By most standards, this is mild-to-moderate sleep apnea,” Winter explains. “Patients in my clinic are often far higher than this in terms of severity.” (He says the highest number he’s seen is 155 breathing problems per hour.) “It is worth noting that this is a very mild population of sleep apnea patients and not reflective of the general sleep apnea population in a sleep clinic,” Winter says.
In that trial, AD109 dropped breathing problems from about 20 per hour to about 11 per hour. “Stated another way, they went from having mild-to-moderate sleep apnea to having mild sleep apnea,” Winter says. “While they got 50 percent better, they still have sleep apnea.”
He compares that to taking a pill that makes vision 50 percent better. “Miracle? Not really,” Winter says. “It makes my 20/200 vision 20/100...and despite the miracle pill, I still need glasses.”
Praveen Rudraraju, MD, medical director of the Center for Sleep Medicine at Northwell’s Northern Westchester and Phelps hospitals, notes that this doesn’t mean people on the medication would automatically be able to stop using a CPAP machine, if they already use one. “If AD109 is approved, I would consider it for patients with mild obstructive sleep apnea or for those who have failed CPAP therapy,” he says. “CPAP would continue to be recommended as the first-line treatment, given its established effectiveness and minimal side-effect profile.”
CPAP machines are often considered a first-line therapy for sleep apnea because they help to keep the airways open. “But many people have difficulty using CPAP because the machines are noisy, the masks can be irritating to wear, and side effects—gas and stomach discomfort due to swallowing air—can occur,” Johnson-Arbor says. “Only 40 to 60 percent of patients who are prescribed CPAP can actually tolerate it over long-term use. Because of this, researchers have investigated medications that target sleep apnea as an alternative treatment to CPAP machines.”
Winter agrees that AD109 will likely be a better choice for people with mild sleep apnea or who can’t use CPAP, undergo surgery, or use an oral appliance. “It is not going to be a particularly useful medication for the vast majority of sleep apnea patients,” he says. “At the end of the day, we ideally want all of our sleep apnea patients to not just be ‘better,’ we want their breathing disturbances to be as normalized as possible.”
One more thing to consider: The injectable medication Zepbound is FDA-approved for treating moderate-to-severe obstructive sleep apnea in adults with obesity. (Obesity and sleep apnea often occur together.) Clinical trial results, which looked at patients with moderate to severe sleep apnea, were more pronounced. “By the end of the trial, about 50 percent no longer met the criteria for sleep apnea and therefore no longer needed treatment. They were ‘cured,’” Winter says.
Ultimately, if you have sleep apnea, Winter says it’s best to talk to a healthcare provider about all the options on the table, including medications, CPAP, surgeries, and oral appliances. “The conversation everyone with sleep apnea should be having is a conversation about not only the therapy that is right for that particular situation, but what these therapies can and cannot do,” Winter says.
