Sleep apnea pill reduces breathing events by 44% in phase 3 trial

In the SynAIRgy phase 3 trial, the oral drug AD109, developed by Apnimed, reduced sleep apnea breathing interruptions by 44% over six months. Combining aroxybutynin and atomoxetine, AD109 targets neuromuscular airway collapse, offering a potential alternative for patients unable to tolerate standard CPAP therapy. While 21% of participants discontinued treatment due to mild side effects like dry mouth, Apnimed has submitted an NDA to the FDA, with a potential review decision expected in Q1 2027.

AD109 phase 3 trial results

• ▪The SynAIRgy phase 3 trial of AD109 was conducted across 69 sites in the United States and Canada, involving 646 adults with mild to severe obstructive sleep apnea
• ▪Participants receiving a placebo in the SynAIRgy trial experienced an 18% reduction in their apnea-hypoxia index, compared to the 44% reduction seen in the AD109 group
• ▪In the SynAIRgy phase 3 trial, 40% of participants taking AD109 improved enough to move to a less severe obstructive sleep apnea category, and 18% achieved complete disease control
• ▪In the SynAIRgy phase 3 trial, the oral medication AD109 reduced the apnea-hypoxia index (breathing interruptions per hour) by approximately 44% over six months

AD109 dual-drug composition

• ▪The oral medication AD109 is a combination of two drugs, aroxybutynin and atomoxetine, designed to support throat muscles and prevent airway collapse during sleep
• ▪The study detailing the dual-drug composition and trial results of AD109 was published in the American Journal of Respiratory and Critical Care Medicine

CPAP treatment gap

• ▪Dr. Patrick John Strollo of the University of Pittsburgh Medical Center stated that an oral pill like AD109 could address the treatment gap for patients unwilling or unable to use CPAP
• ▪Continuous Positive Airway Pressure remains the gold standard treatment for obstructive sleep apnea, but many patients remain untreated or undertreated due to difficulty tolerating the device

Side effects profile

• ▪Approximately 21% of participants in the SynAIRgy phase 3 trial discontinued the AD109 treatment due to side effects
• ▪The most frequently reported side effects of AD109 in the phase 3 trial were dry mouth, nausea, insomnia, and difficulty urinating

FDA Fast Track designation

• ▪Apnimed has submitted a New Drug Application for AD109 to the FDA, expecting a potential PDUFA target action date in the first quarter of 2027
• ▪The U.S. Food and Drug Administration has granted Fast Track designation to AD109 for the treatment of obstructive sleep apnea

Neuromuscular airway collapse mechanism

• ▪AD109 is designed to treat obstructive sleep apnea by targeting the underlying neuromuscular drivers and dysfunction that contribute to airway collapse during sleep
• ▪The clinical findings of the AD109 trial will be published alongside a companion mechanistic review in the American Journal of Respiratory Cell and Molecular Biology

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