Key takeaways:
- Patients with OSA in this phase 3 trial represented a real-world population.
- Those receiving the drug, a first-in-class neuromuscular modulator, showed improvements in apnea-hypopnea index.
Obstructive sleep apnea severity measured via apnea-hypopnea index decreased among patients receiving AD109, an oral combination drug, for 26 weeks, according to phase 3 SynAIRgy trial topline results.
AD109 (Apnimed) is made up of 2.5 mg aroxybutynin, a novel antimuscarinic, and 75 mg atomoxetine, a selective norepinephrine reuptake inhibitor, according to a press release from Apnimed.
Patrick J. Strollo Jr.
“The drug AD109 provides an additional tool in the toolbox for the treatment of OSA that does not require a device (positive pressure via a mask/oral appliance) or a surgical intervention (anatomy altering/upper airway stimulation),” Patrick J. Strollo Jr., MD, FACP, FCCP, FAASM, chair of the SynAIRgy clinical trial and vice chair of medicine for Veterans Affairs at the University of Pittsburgh School of Medicine, told Healio. “As we move toward precision medicine, AD109 may represent an important treatment option for the heterogenous OSA population.”
The options currently available for sleep clinicians to treat OSA are limited, which Apnimed CEO Larry Miller, MD, called “unacceptable for a disease that impacts 80 million Americas.”
“Our topline results represent the future potential, if approved, for a simpler, patient-friendly treatment option for OSA — one that could expand adherence and help address the large population of people with OSA who struggle with or abandon existing therapies,” Miller told Healio.
In the multicenter, randomized, double blind, placebo-controlled, parallel-arm phase 3 SynAIRgy trial, Strollo and colleagues evaluated 646 adults (49.1% women) with mild to severe OSA either intolerant of CPAP therapy or refusing to use it to determine if once-daily oral AD109 before bedtime positively impacts apnea-hypopnea index (AHI) vs. placebo at 26 weeks.
“AD109 is a first-in-class neuromuscular modulator that effectively treats sleep-disordered breathing in both nonrapid eye movement sleep and rapid eye movement,” Strollo told Healio.
Within the study population, 34.4% had mild OSA, 42.4% had moderate OSA and 23.2% had severe OSA. According to the release, multiple racial groups and patients from different weight classes were also represented in this cohort.
“The SynAIRgy study population was diverse with regard to sex and ethnicity that supports generalizability with regard to treatment,” Strollo said.
As Healio previously reported, AD109 lessened OSA severity in the 4-week phase 2b MARIPOSA trial, and this was also observed in the phase 3 trial. At the 26-week mark, researchers found a significantly greater decrease in AHI from baseline among patients receiving AD109 vs. placebo (mean reduction, 55.6%; P = .001).
The release also noted that two measures of oxygenation significantly improved in the AD109 group: hypoxic burden (P < .0001) and oxygenation desaturation index (P = .001).
Of those who received AD109, researchers reported that 51.2% shifted to an OSA disease severity category lower than their baseline category. Further, an AHI of less than five events per hour was deemed complete OSA disease control and was achieved by 22.3% of the AD109 group, according to the release.
“The topline data demonstrate a highly significant improvement in the AHI across all classes of disease severity,” Strollo told Healio.
Notably, unlike Zepbound (tirzepatide, Eli Lilly), an FDA-approved prescription medicine for adults with moderate to severe OSA and obesity, Strollo said AD109’s mechanism of action is not dependent on weight loss.
“OSA is a ‘bicomponent’ disease caused in almost all patients by a narrowed upper airway and neuromuscular dysfunction of the pharyngeal musculature,” Miller told Healio. “GLP-1 drugs address airway narrowing due to obesity but do not affect pharyngeal muscles. AD109 acts directly to correct the neuromuscular dysfunction.
“Also, a point that is frequently misunderstood is that the majority of patients with OSA are not obese, and thus GLP-1 drugs are not indicated in these patients,” Miller added.
In terms of safety, the release said that the drug was “generally well-tolerated.” Those receiving AD109 had no serious adverse events related to the drug, and researchers observed adverse events that aligned with past trials assessing AD109. In the MARIPOSA trial, frequent negative outcomes included dry mouth, insomnia and nausea.
“It is reassuring that the phase 3 SynAIRgy topline results provide more definitive safety and efficacy data,” Strollo said.
“Pulmonologists and other sleep specialists can use these findings to start thinking about how future oral treatments targeting the neuromuscular root cause of OSA might expand their toolbox — particularly for patients who are unable to tolerate existing options — so they can be ready to personalize care as the treatment landscape evolves,” Miller told Healio.
According to the release, clinicians can expect to see full SynAIRgy findings at a future medical congress and in a peer-reviewed scientific journal.
“We plan to submit the data for regulatory review by the FDA in early 2026,” Miller said.
Additionally, Miller said another phase 3 trial on AD109 that will look at outcomes at 1 year is underway, and topline results of this trial are expected in quarter three.
“Like SynAIRgy, the LunAIRo trial has been designed to reflect the real-world diversity of people living with OSA — providing additional insights into how AD109 may perform across a broad range of patients, spanning a wide range of disease severity, weight classes, racial and ethnic backgrounds, ages and genders,” Miller told Healio. “We believe this is an important differentiator in sleep medicine research, where inclusivity remains a critical factor in evaluating therapeutic impact.”
For more information:
Patrick J. Strollo Jr., MD, FACP, FCCP, FAASM, can be reached at strollopj@gmail.com.
Larry Miller, MD, can be reached at media@apnimed.com.
