Oral drug combination lowers OSA severity over 51 weeks

Key takeaways:

• AD109 is taken orally and once daily before bedtime.
• Topline results from two phase 3 trials have shown that AD109 lowers OSA severity.
• Apnimed plans to present AD109 to the FDA via a new drug application.

Obstructive sleep apnea severity measured via apnea-hypopnea index decreased among patients receiving AD109, an oral combination drug, for 51 weeks, according to phase 3 LunAIRo trial topline results.

“The LunAIRo trial demonstrated a 46.8% reduction in apnea-hypopnea index (AHI) sustained over 12 months, which offers potential promise as a novel treatment strategy for treating patients with OSA,” Sanjay Patel, MD, primary investigator for the LunAIRo clinical trial and director of the UPMC Comprehensive Sleep Disorders Clinical Program, told Healio.

AD109 (Apnimed) is made up of 2.5 mg aroxybutynin, a novel antimuscarinic, and 75 mg atomoxetine, a selective norepinephrine reuptake inhibitor, according to an Apnimed press release.

As Healio previously reported, AD109 also decreased OSA severity in the phase 3 SynAIRgy trial. Patel said both trials had similar design, treatment population and primary endpoint, but the LunAIRo trial had a longer treatment period (1 year vs. 6 months).

“Conducting two independent trials is important in ensuring that any trial results are robust and not a chance occurrence,” Patel told Healio.

In the multicenter, randomized, double blind, placebo-controlled, parallel-arm phase 3 LunAIRo trial, Patel and colleagues assessed 660 adults (46% 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 AHI vs. placebo at 26 and 51 weeks.

Within the study population, 37% had mild OSA, 33% had moderate OSA and 30% had severe OSA. According to the release and Patel, multiple racial groups and patients from different weight classes were also represented in this cohort.

At the 26-week mark, researchers found a significantly greater decrease in AHI from baseline among patients receiving AD109 vs. placebo (mean, 46.8% vs. 6.8%; P < .001), and this was also true at the 51-week mark. For comparison, the mean reduction in AHI at 26 weeks among those receiving AD109 in the SynAIRgy trial was 55.6%.

“The finding that the improvements in AHI were very similar between SynAIRgy and LunAIRO is reassuring that these findings are real,” Patel told Healio.

Of those who received AD109, researchers reported that the proportion of patients who shifted to an OSA disease severity category lower than their baseline category was 45% at week 26 and 47.5% at week 51. Similarly, the proportion of patients in the AD109 group who achieved a decrease in AHI by at least 50% from baseline reached significance at both times (both P < .0001).

Further, an AHI of less than five events per hour was deemed complete OSA disease control and was achieved by 22.9% of the AD109 group at week 26 and 22.5% at week 51, according to the release.

“Results to date suggest the improvements in AHI were present across levels of obesity and sleep apnea severity,” Patel said. “We still await analysis of symptom responses to understand which patient populations this drug may be useful in helping. But overall, these data suggest AD109 may be useful in helping a broad range of patients who have not been able to successfully use CPAP.”

Researchers also found that two measures of oxygenation significantly improved in the AD109 group at both evaluated times: hypoxic burden (P < .0001) and oxygen desaturation index (P < .001).

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 treatment-emergent adverse events that aligned with past trials assessing AD109.

“The 1-year follow-up in LunAIRo helps demonstrate that the effects on AHI are sustained long term and also that there are no new worrisome signals about the drug’s safety,” Patel told Healio.

According to the release, clinicians can expect to see more findings from both LunAIRo and SynAIRgy at a medical congress this year.

Apnimed also highlighted in the release that they are planning to submit a new drug application to the FDA for AD109 based on both these trials by early 2026.

Reference:

• 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. https://apnimed.com/article/ad109phase3toplineresults/. Published May 19, 2025. Accessed July 25, 2025.

For more information:

Sanjay Patel, MD, can be reached at pulmonology@healio.com.