Could We Treat Obstructive Sleep Apnea with a Pill?
Apnimed releases its pivotal Phase 3 data on AD109 oral OSA treatment
For decades, the standard upfront treatment for obstructive sleep apnea (OSA) has been continuous positive airway pressure (CPAP) therapy. While very effective, CPAP machines are cumbersome and uncomfortable, and > 50% of patients ‘fail’ long-term adherence/tolerance. There is a huge need for additional treatment modalities given the significant prevalence and burden of OSA.
Now, a potential breakthrough in OSA treatment is on the horizon: a pill that could serve as primary OSA treatment.
Introducing AD109: A Novel Oral Therapy
Apnimed, a pharmaceutical company specializing in sleep-related breathing disorders, has shown promising results with its drug AD109, an oral medication designed to treat OSA. AD109 is a combination of two agents: atomoxetine, a selective norepinephrine reuptake inhibitor (NRI) and aroxybutynin, a novel antimuscarinic agent. These compounds act to increase central stimulation of upper airway muscle dilators (primarily the genioglossus), thus maintaining airway patency during sleep. Aroxybutynin also seems to help decrease arousal threshold and thus limit sleep-disruptions during the night.
The end result: an overall decrease in sleep apnea events. But how well would it work in patients?
Clinical Trials and Progress
AD109 first came on my radar a couple years ago when it published its Phase 2b MARIPOSA trial data. This Phase 2b trial showed one-month long treatment impacts of AD109: patients experienced significant reductions in the Apnea-Hypopnea Index (AHI) from ~20 to 10 events, with 44% having a greater than 50% decrease. Participants also reported significant improvements in quality of life symptoms. Most importantly, the medication appeared safe with minimal side effects. From this, a larger and lengthier study was proposed, and I have been monitoring the company’s product since.
Yesterday, Apnimed announced positive topline results across the board for this Phase 3 SynAIRgy trial:
646 participants across a geographically diverse set of medical centers in the U.S. and Canada. Broad representation of weights, sex, and ethnicities. Also a broad range of OSA severity: 35% mild, 42% moderate, 23% severe.
Randomized, double-blind, placebo controlled trial of AD109. The “Gold Standard” of medical therapy trials.
Statistically significant improvement in AHI, mean reduction of 56%. Significant improvements in hypoxic burden/ODI measures, 51% of patients with reduction in their severity category. 22% ‘cure’ of OSA with decrease to AHI < 5.
Well tolerated, no serious adverse events.
In short, home-run results that advance their drug toward FDA approval.
The Road Ahead
Apnimed plans to submit a New Drug Application to the FDA by early 2026. The company also has a 1-year trial ongoing and will present that data later this year. If (when, based on their data so far) approved, AD109 could become the first oral pharmacologic treatment for OSA, offering a convenient alternative to current therapies.
Rough estimates are that 10-20% of the U.S. population has OSA (varying on definition/severity). Studies and real world experience approximate 50% of OSA patients don’t use CPAP long-term. These patients WANT alternatives. While surgery and weight loss (and GLP’s) are still worthwhile options, the convenience of a once-daily pill with real efficacy and solid safety profile would be very compelling.
In their prior studies, a decrease in REM-sleep had been reported in the AD109 group. That was something I am keeping an eye on, though my brief online search indicated that minimizes with time. Similarly, there are potential sleep architecture changes that are possible on this medication- that will probably be a side-effect to monitor once these come to market.
Overall, very exciting time for clinicians and patients. Last week, we presented the new surgical options likely to be FDA approved this year (deemed the Inspire 2.0 class). And now, an oral pill that can significantly improve OSA. I look forward to continuing to share ongoing updates in the business, tech, and practice of OSA.
Best, Chris.