Once-Daily Oral Pill for Obstructive Sleep Apnea Shows Promising Phase 3 Results, Paving Way for FDA Submission

Author(s):

Key Takeaways

AD109, a first-in-class oral pill, significantly reduced AHI in OSA patients, meeting the primary endpoint in the SynAIRgy trial.
The trial included 646 adults intolerant of CPAP, showing improvements in hypoxic burden and oxygen desaturation index.
AD109 targets the hypoglossal motor nucleus, enhancing noradrenergic signaling and reducing muscle relaxation to maintain airway patency.
Apnimed plans to submit an NDA to the FDA in 2026, with further results from the LunAIRo trial expected in Q3 2025.

Apnimed's AD109 shows promise in treating obstructive sleep apnea, achieving significant results in a landmark Phase 3 trial, paving the way for FDA approval.

Larry Miller, MD

Newly announced results from the phase 3 SynAIRgy trial (NCT05813275) showed that AD109 (Apnimed), a first-in-class, once-daily oral pill, met its primary end point in reducing apnea-hypopnea index (AHI) across a broad range of patients with mild, moderate, and severe obstructvie sleep apnea (OSA). Based on these findings, Apnimed plans to submit a new drug application (NDA) to the FDA in early 2026 for AD109 as a potential treatment of OSA.¹

Considered the largest such drug trial for OSA, SynAIRgy included 646 adults with the disease who were intolerant of or currently refusing continuous positive airway pressure (CPAP). Coming into the study, 34.4% of patients had mild OSA, 42.4% had moderate, and 23.2% had severe. Overall, treatment with AD109, a fixed dose combination of aroxybutynin 2.5 mg/atomoxetine 75 mg, led to a statistically significant change in AHI, the primary end point, over a 26-week period relative to placebo (P = .001).

Full data from the study is expected to be presented at a medical congress later this year and published in a peer-reviewed scientific journal. AD109, a unique agent, targets the hypoglossal motor nucleus, a key neural center responsible for controlling upper airway dilator muscles. By enhancing noradrenergic signaling through atomoxetine and reducing muscle relaxation via aroxybutynin, the agent aims to maintain upper airway patency during sleep, thereby preventing apneic events.

"Today is a landmark moment for Apnimed and for millions living with OSA who have long struggled with limited treatment options,” Larry Miller, MD, chief executive officer at Apnimed, said in a statement.¹ “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. We believe these results represent the dawn of a new era in the OSA treatment paradigm."

He added, "We are deeply grateful to the patients, investigators, and clinical teams whose partnership and commitment made this achievement possible. Importantly, these results increase our confidence in the expected outcome of the second Phase 3 clinical trial, LunAIRo, with topline results expected in Q3’25."

In SynAIRgy, patients underwent a polysomnogram on treatment at week 4. Overall, treatment with the oral agent led to meaningful improvements in oxygenation, as assessed by hypoxic burden (P <.0001), and oxygen desaturation index (P = .001). Furthermore, 51.2% of treated patients experienced a reduction in OSA disease severity, and 22.3% achieved complete disease control, defined as an AHI of fewer than 5 events per hour.

With the promising data, the clinical community will await additional results from LunAIRo, a double-blind, placebo-controlled study (NCT05811247) of AD109 in mild to severe OSA, later this year. The trial, made up of 660 participants, is a parallel-arm study lasting 1 year, using reduction of airway obstructions–defined through AHI–as the primary end point. Comprising individuals who are intolerant of or currently refusing PAP therapy, LunAIRo will also teste several other secondary end points, including effect on OSA symptoms using the PROMIS-Fatigue scale, as well as other standard objective and subjective metrics of OSA.²

Patrick Strollo, MD, FACP, FCCP, FAASM

"These Phase 3 topline results are highly encouraging and represent the potential for a much-needed innovation in the treatment of OSA,” study chair Patrick Strollo, MD, FACP, FCCP, FAASM, a pulmonologist at the University of Pittsburgh, said in a statement.¹ "For too long, progress in OSA has been limited, leaving many people with OSA without sustainable treatment options. 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."

AD109 first demonstrated its therapeutic effects in the phase 2 MARIPOSA trial (NCT05071612), a 211-patient cohort that was randomized to either AD109, atomoxetine, or placebo. Results from the study showed that AHI4 was reduced from a median of 20.5 to 10.8 events/hour in the AD109 2.5 mg/75 mg dose, resulting in a statistically significant difference vs placebo (P <.001).³

Additional findings from the study showed that 41% of AD109-treated participants who completed the trial achieved an apnea-hypopnea index (AHI) below 10, 44% had a greater than 50% reduction from baseline, and 15% experienced reductions of 80% or more; notably, atomoxetine alone failed to improve daytime OSA symptoms and significantly worsened nighttime sleep quality, confirming its inadequacy as monotherapy. AD109 also led to statistically significant improvements in daytime functioning, as measured by PROMIS-Fatigue (P <.05), and showed favorable trends on PROMIS-Sleep Impairment and PROMIS-Sleep Disturbance, further supporting its potential as a comprehensive treatment for OSA.