Investigational Oral Medication for OSA Meets Primary Endpoints in Phase 3 Clinical Trial

AD109, a novel investigational oral medication for obstructive sleep apnea (OSA), met its primary endpoint in a pivotal phase 3 clinical trial, showing a mean reduction in apnea-hypopnea index (AHI) of 55.6% from baseline at 26 weeks compared to placebo (P =.001), according to topline results reported by Apnimed in a May 19 statement.

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Participants treated with AD109, a combination of aroxybutynin 2.5mg and atomoxetine 75mg, who represented a broad range of OSA severity, also achieved significantly improved oxygenation, the company said, and half (51.2%) demonstrated a reduction in category of OSA disease severity. Approximately 1 in 5 (22.3%) AD109-treated participants achieved complete OSA disease control (defined as AHI of fewer than 5 events/hour), according to the statement.

The first-in-class AD109 represents a potential paradigm shift in OSA treatment. The medication targets the neuromuscular dysfunction that causes upper airway collapse during sleep, addressing a root cause of the condition that affects an estimated 25% to 30% of men and 9% to 17% of women in the US (~80 million Americans) and one billion people worldwide.²

"Today is a landmark moment for Apnimed and for millions living with OSA who have long struggled with limited treatment options," Larry Miller, MD, Apnimed CEO said in the statement. "The positive results from our phase 3 SynAIRgy trial bring us closer to realizing our vision of offering a simple, safe, and effective oral drug — one that is grounded in science, driven by unmet need, and centered on people with OSA."

The SynAIRgy trial enrolled 646 adults across 73 centers in the US and Canada, making it the largest phase 3 clinical trial of a medication to treat OSA, according to Apnimed. Participants were either intolerant of or currently refusing therapy with continuous positive airway pressure (CPAP). Apnimed emphasized that the final cohort was representative of a real-world patient population, with profiles typically seen in a sleep clinic population: 49.1% women, multiple racial/ethnic groups, varied weight classes, and OSA severity levels including mild (34.4%), moderate (42.4%), and severe (23.2%).

Beyond the primary endpoint, AD109 demonstrated improvements in secondary and exploratory endpoints, including significant enhancements in oxygenation as measured by hypoxic burden (P <.001) and oxygen desaturation index (P =.001).

In the Apnimed statement, Patrick Strollo, Jr, MD, study chair of the SynAIRgy clinical trial and vice chair of medicine for Veteran's Affairs at the University of Pittsburgh School of Medicine, called the results "highly encouraging" and noted they "represent the potential for a much-needed innovation in the treatment of OSA."

"For too long, progress in OSA has been limited, leaving many people with OSA without sustainable treatment options," Strollo said. "The results from SynAIRgy suggest that if approved, AD109 could offer a compelling new treatment option — a novel oral drug that targets the neuromuscular root cause of airway obstruction in sleep apnea and holds promise for transforming care for a broad range of patients."

The medication was generally well-tolerated, with adverse events consistent with earlier clinical trials. No serious adverse events related to AD109 were reported in the SynAIRgy trial.

OSA should be considered a top public health priority," Monica Mallampalli, PhD, president and CEO of the Alliance of Sleep Apnea Partners, said in the statement. "It as a serious, common, chronic disease that affects a wide range of people, impacting both males and females of all age groups, ethnicities, and weight classes, including those with or without obesity."

Apnimed expects topline results from its second phase 3 clinical trial, LunAIRo, in the third quarter this year. According to the statement, the company plans to submit a New Drug Application to the FDA by early 2026. Full data from the SynAIRgy trial will be presented at a medical congress later this year and published in a peer-reviewed scientific journal.

The AD109 mechanism of action represents a novel approach to OSA treatment. The combination leverages aroxybutynin, a novel antimuscarinic, and atomoxetine, a selective norepinephrine reuptake inhibitor, to target the underlying neurobiology of the hypoglossal motor nucleus. This approach increases signals to the upper airway muscles during sleep, potentially preventing collapse without requiring external devices like CPAP machines.

"In a disease characterized by complex and invasive treatment options, AD109 may be a simple solution to help improve oxygenation and health wellbeing for people living with OSA," Apnimed concluded.

Reference

1. Apnimed announces positive topline results in the first landmark phase 3 clinical trial of AD109, an investigational once-daily oral pill for obstructive sleep apnea. News release. Apnimed. May 19, 2025. Accessed May 20, 2025. Available at: https://apnimed.com/article/ad109phase3toplineresults/

2. Slowick JM, Sankari A, Collen JF. Obstructive sleep apnea. StatPearls. Updated March 4, 2025. Accessed May 20, 2025. https://www.ncbi.nlm.nih.gov/books/NBK459252/