Could We Treat Obstructive Sleep Apnea with a Pill? Part 2
Apnimed releases Phase 3 LunAIRo trial results for AD109, its promising oral OSA drug
Earlier this year, I wrote about Apnimed’s investigational combination therapy, AD109, a nightly pill designed to treat obstructive sleep apnea (OSA). That post explored the mechanism and the promise seen in early study results. Now, we have fresh data—topline results from an additional Phase 3 trial—and they’re worth exploring.
So, let’s get into it. Did the drug deliver? Will this reshape how we think about OSA treatment? And what are the caveats?
A Quick Refresher: What Is AD109?
AD109 is a combination of two agents:
Atomoxetine: A selective norepinephrine reuptake inhibitor
Aroxybutynin: A novel antimuscarinic
Together, these drugs are designed to increase airway patency, particularly through the genioglossus, which plays a key role in maintaining airway patency during sleep. Aroxybutynin also seems to help decrease arousal threshold and thus limit sleep-disruptions during the night.
The net effect is improvement in OSA.
What the New Phase 3 Data Show
Apnimed just released topline results from a Phase 3 trial (called LunAIRo):
-Study is a 12 month, double-blind, placebo-controlled study. The “Gold Standard” of medical therapy trials.
🔹 Primary endpoint met
AD109 produced a statistically significant and clinically meaningful reduction in AHI compared to placebo over 26 weeks (mean reduction 47% vs. 7% placebo.
The press-release mentions this remained significant at 51 weeks, but doesn’t indicate % reduction at that time point.
🔹 Multiple secondary endpoints met
Significant reductions in hypoxic burden at 26 and 51 weeks.
Improved severity score in 47% of patients at 51 weeks.
🔹 Safety profile was acceptable, no serious adverse events. Similar to prior studies.
🔹 The population studied was a diverse grouping of sex, weights, severity of OSA, and ethnicities - enhancing the applicability of the trial results.
This builds upon AD109’s success in its prior SynAIRgy Phase 3 study with similar results. The company plans a New Drug Application (NDA) with the FDA in early 2026.
A Few Important Caveats
Of course, a pill isn’t a panacea. Here are a few considerations to keep in mind:
Not all OSA is alike: AD109 targets collapsibility via muscle tone, and perhaps some arousal threshold improvements. While the numbers are overall encouraging, there is still meaningful OSA in a large proportion of treated patients. Additional sub-analysis is needed: I suspect very severe OSA and more obese patients respond less. This is similar to our usual ‘phenotyping’ of OSA in practice and surgery, where we tailor our therapies accordingly.
Limited discussion of subjective measures: Previous Phase 2b press-releases about AD109 mention improvement in patient sleepiness scores; this study didn’t mention. I look forward to additional data around not just OSA numbers, but impact on patients’ sleep quality.
More information on side effects: Thus far it seems that AD109 side effects are fairly mild. Atomoxetine does cause insomnia in some patients. Dry mouth seems to be the most common side effect overall.
Why This Matters
If approved, AD109 would be the first oral pharmacologic treatment specifically for OSA. Tens of millions of patients have OSA. Many of these patients struggle with CPAP and are looking for alternatives. If (when, based on the data so far) the medication is approved, it represents a compelling alternate treatment option for patients.
We’re not replacing CPAP, and there is still space for alternatives like oral appliances and surgeries. But this would definitely expand the toolbox.
We will look forward to following the company’s progress. Until then, thanks for supporting and sharing the newsletter:
—Chris