Apnimed’s star sleep apnea asset has hit the latest landmark on its march down victory road. The Massachusetts biotech reported May 19 that AD109 met the primary endpoint of a phase 3 trial, reducing sleep apnea severity by a statistically significant 55.6% compared to baseline.
Sleep apnea severity was measured using the apnea-hypopnea index, which is the average number of times a patient either stops breathing or experiences shallow breathing per hour while sleeping.
The phase 3 SynAIRgy trial is a randomized, double blind, placebo-controlled trial that evaluated improvement in obstructive sleep apnea (OSA) symptoms after six months of daily bedtime doses of AD109. The drug is a combination of aroxybutynin, a novel antimuscarinic, and atomoxetine, a noradrenaline reuptake inhibitor (NRI) that is also used in ADHD. The trial enrolled 646 participants.
There were no serious adverse events related to AD109 in the trial, Apnimed said in the release, with the safety profile resembling that of the candidate’s earlier, also successful phase 2 trial.
These results have Apnimed ready to submit a new drug application to the FDA by early 2026, according to the release. The biotech has already been preparing for AD109’s potential commercial launch, hiring Pfizer veteran Graham Goodrich, architect of the marketing for migraine drug Nurdec ODT, as chief commercial officer in January 2024.
“We believe these results represent the dawn of a new era in the OSA treatment paradigm,” Apnimed CEO Larry Miller, M.D., said in the release. “Importantly, these results increase our confidence in the expected outcome of the second phase 3 clinical trial, LunAIRo.”
LunAIRo is similar to SynAIRgy but is studying AD109’s effectiveness after one year instead of six months. Results from this second phase 3 trial are expected next quarter, Miller said.
In addition to hitting its primary endpoint, AD109 also significantly improved patients’ oxygenation, as measured by hypoxic burden and oxygen saturation index, and 22.3% of participants who received the drug candidate saw their OSA completely controlled, defined as fewer than five apnea events per hour while asleep.
OSA occurs when the throat muscles relax and block airflow during sleep. This disruption can cause patients to wake and gasp for air at night, snore loudly and overall get worse sleep. The drops in oxygen flow can also boost blood pressure, increasing the risk of heart problems.
Sleep apnea is most commonly treated with a CPAP machine, a device that pumps air through a mask during sleep so pressure in the airway doesn’t drop low enough for muscles to collapse. AD109 instead goes for the source of the problem, targeting the motor neurons that control breathing during sleep and upping their activity so the throat muscles don’t relax.
This condition affects about 80 million people in the U.S. and 1 billion worldwide, Apnimed said in the release, but has no approved drugs designed specifically to treat it. Eli Lilly’s weight loss drug Zepbound (tirzepatide) scored the first ever FDA nod for a prescription sleep apnea medicine in December 2024 but is only approved for adults with obesity.
“OSA should be considered a top public health priority: it is a serious, common, chronic disease that affects a wide range of people,” Monica Mallampalli, Ph.D., president and CEO of the Alliance of Sleep Apnea Partners, said in the release. “The SynAIRgy results offer people hope that an oral therapy is on the horizon that could make it easier for them to manage their OSA and reclaim their lives.”