Standard treatment for breathing problems caused by obstructive sleep apnea is a medical device. But many people find it uncomfortable to wear the mask that comes with a continuous positive airway pressure (CPAP) machine. Apnimed’s experimental drug could provide an easier alternative, and this pill now has results from a pivotal study the startup says support plans for an FDA submission. It could end up challenging a big pharmaceutical giant.
Apnimed’s approach to obstructive sleep apnea (OSA) is to target muscles you probably didn’t realize you have. The condition, which affects an estimated 80 million people in the U.S., results in repeated collapse of the upper airway during sleep, causing breathing interruptions and intermittent periods of oxygen deprivation. Anatomical abnormalities contribute, and surgery offers a way (albeit, an invasive one) to address the condition. Another contributor to OSA is dysfunction of muscles that control the airway.
The Apnimed drug, AD109, combines two compounds: the company’s novel antimuscarinic small molecule named aroxybutynin, and the old attention-deficit/hyperactivity disorder medication atomoxetine (brand name Strattera). This pairing is formulated as a single pill taken each night before bed. According to Cambridge, Massachusetts-based Apnimed, the synergistic effect of AD109’s two pharmaceutical ingredients targets neurological pathways to activate muscles in the upper airway to keep it open during sleep. AD109 came from a Brigham & Women’s Hospital (BWH) discovery that this combination was effective for treating OSA, Apnimed co-founder and CEO Larry Miller said in an email. That discovery aligned with prior research suggesting that these drug classes can modulate activity in the part of the brain that controls the upper airway muscles.
“In early studies at BWH where electrodes were placed in the tongue muscle during sleep, researchers were able to show directly that these drug classes can increase muscle tone in the upper airway and reduce airway obstructions,” Miller said.
The trial results announced Monday are from a Phase 3 test that enrolled 646 adults in the U.S. and Canada who have mild, moderate, or severe OSA and either cannot tolerate CPAP therapy or refuse it. Participants were randomly assigned to receive the study drug or a placebo to be taken nightly. The main goal was to measure at six months the change in the apnea-hypopnea index, a scale used to measure the breathing reductions or interruptions during sleep (the higher the score, the more severe the OSA).
Apnimed reported an average 55.6% reduction in apnea-hypopnea index scores in the study drug arm along with “significantly improved oxygenation and reduced disease severity.” For the placebo arm, the average reduction in scores was 19%. The company said AD109 was generally well tolerated and adverse events were consistent with earlier tests. The most common adverse events reported from a four-week Phase 2 study were dry mouth, insomnia, and urinary hesitancy.
Apnimed said full Phase 3 results will be presented at a medical meeting later this year and published in a peer-reviewed journal. The development program for AD109 includes a second Phase 3 trial testing the drug in OSA patients for one year. Apnimed expects preliminary data from this study in the third quarter of 2025. With data from the two studies, the company plans an FDA submission for AD109 in early 2026. Miller noted that OSA affects more than 1 billion people in the world. Apnimed plans to explore ways to make AD109 available to those patients as well, he said.
A sleep apnea drug is already available in the U.S. Late last year, Eli Lilly’s blockbuster obesity medication, Zepbound, expanded its label, becoming the first FDA-approved drug for moderate-to-severe OSA. The once-weekly injectable peptide is designed to bind to two gut receptors to spark metabolic effects, such as weight loss. The way Zepbound works to treat OSA is unknown, but obesity is a risk factor for the disorder. Zepbound’s OSA trial results showed patients lost weight. This weight reduction is thought to improve sleep apnea.
Despite being the first drug to market for OSA, Zepbound faces hurdles in this indication. Manufacturing peptide drugs is expensive. Also, many patients prefer pills to injections. As a small molecule, AD109 is less expensive to manufacture and will be available as a more patient-friendly pill. But Apnimed is not the only company developing oral OSA drugs.
Incannex Healthcare has reached Phase 2/3 testing with IHL-42X, a combination of two older medicines: acetazolamide, which is a carbonic anhydrase inhibitor whose FDA-approved uses include treating glaucoma and epilepsy, and dronabinol, a synthetic cannabinoid approved for treating nausea, vomiting, and appetite loss. Separately, both drugs have clinical data showing reductions in the apnea hypopnea index. The company believes dronabinol’s activity on cannabinoid receptors causes the airway to dilate. Meanwhile, acetazolamide signals to the body that there is excess carbon dioxide in the blood, which has the effect of increasing respiration.
“By combining two agents with mechanisms known to reduce [apnea-hypopnea index] in one pharmaceutical formulation, we believe IHL-42X may have therapeutic benefit at lower doses of each constituent drug that are safe and tolerable,” the company said in its annual report.
Melbourne, Australia-based Incannex is conducting the Phase 2 portion of IHL-42X’s clinical trial in the U.S.; the expanded Phase 3 part will include the United Kingdom and the European Union. The company expects preliminary Phase 2 data in the first half of this year.
Apnimed has its own carbonic anhydrase inhibitor for OSA. Last month, it acquired global rights to sulthiame from German company Desitin Arzneimittel, which had completed Phase 2 testing of the drug in OSA. Sulthiame is already available in some countries as an epilepsy medication. Miller said this oral small molecule gives Apnimed an OSA drug candidate that works differently than AD109. The company will develop this drug for OSA and other sleep disorders through a joint venture with Shionogi.
Apnimed’s last financing was in 2023, when it raised nearly $80 million, extending its Series C round to $142.2 million to fund AD109’s Phase 3 development. The company says it has raised $270 million to date.
Photo: yanyong, Getty Images
