Summary: AD109, a novel once-nightly oral treatment combining aroxybutynin and atomoxetine, met its primary endpoint by significantly reducing AHI in a pivotal phase 3 trial for OSA.
Key takeaways:
- AD109 is a first-in-class combination therapy targeting neuromuscular tone in the upper airway during sleep.
- In the phase 3 study, AD109 achieved a statistically significant reduction in AHI vs placebo, continuing the success seen in the phase 2b MARIPOSA trial.
- AD109 has demonstrated a favorable safety and tolerability profile across over 15 prior Phase 1 and 2 trials.
- Two pivotal trials—LunAIRo and SynAIRgy—are underway to assess the therapy across mild, moderate, and severe OSA.
Apnimed Inc today announced positive topline results from its second pivotal phase 3 clinical trial of its lead candidate AD109 (aroxybutynin 2.5mg/atomoxetine 75mg). LunAIRo was a 12-month study that evaluated the efficacy and safety of AD109 in adults with mild, moderate, and severe obstructive sleep apnea (OSA), across a wide range of weight classes, with the primary endpoint determined at 26 weeks.
AD109 is designed to be the first pharmacological treatment to improve oxygenation during sleep by directly addressing the neuromuscular root cause of upper airway collapse in people with OSA. It is a first-in-class anti-apneic neuromuscular modulator, combining aroxybutynin, a novel antimuscarinic, and atomoxetine, a selective norepinephrine reuptake inhibitor.
The LunAIRo study is a randomized, double blind, placebo-controlled, parallel-arm one-year clinical trial of AD109, an investigational fixed-dose combination of aroxybutynin 2.5mg/atomoxetine 75mg, in participants with OSA who are intolerant of or refuse CPAP. The primary endpoint was assessed at 26 weeks, as with the SynAIRgy phase 3 trial. The trial enrolled 660 adult participants from 64 centers in the United States. Participants were randomized 1:1 to either AD109 or placebo (AD109, n=329; placebo, n=331) and instructed to take their assigned treatment once-daily before bedtime.
Enrolled participants in LunAIRo were representative of the real-world OSA population, including the diverse demographic composition of the United States and the typical profiles seen in a sleep clinic population. Participants included 46% females, multiple racial groups, and varied weight classes spanning healthy weight, overweight, and with obesity. Participants were distributed across OSA severity levels, including mild (37%), moderate (33%), and severe (30%). Participants had symptoms reflective of the OSA patient experience.
Primary Endpoint Met
The LunAIRo trial met its primary endpoint, demonstrating clinically meaningful and statistically significant reductions in airway obstruction at 26 weeks. Participants treated with AD109 achieved a mean reduction in AHI of 46.8% from baseline at week 26 (vs 6.8% with placebo; p<0.001). The reduction in AHI remained significant at the end of the study (week 51, p<0.001). AD109 was generally well-tolerated, with the most common treatment-emergent adverse events being mild or moderate in severity and consistent with prior studies. No serious adverse events related to AD109 were reported in the LunAIRo trial.
The LunAIRo topline results align with the positive topline results previously reported from Apnimed’s SynAIRgy phase 3 clinical trial, which the company believes support the safety and efficacy of AD109 in treating adults with mild, moderate, and severe OSA, subject to review by the Food and Drug Administration (FDA).
“Given the scale of unmet need in OSA, where the majority of patients remain untreated, we believe AD109, as a simple once-daily oral drug, has the potential to expand and reshape the treatment landscape, which would represent a significant commercial opportunity for Apnimed,” says Larry Miller, MD, Apnimed CEO, in a release. “Based on the phase 3 data from LunAIRo and SynAIRgy, Apnimed plans to file a New Drug Application (NDA) with the US FDA in early 2026. As we prepare for FDA regulatory filing and commercialization of AD109, we’re focused on ensuring we have the capabilities, people, and partnerships in place to bring this innovative drug to patients suffering from OSA and the clinicians who treat them.”
Secondary and Exploratory Endpoints
In addition to meeting the primary endpoint, AD109 demonstrated improvements in other topline secondary and exploratory endpoints in the LunAIRo study. Apnimed highlights the following:
- Meaningful improvements in oxygenation as assessed by reductions in hypoxic burden (p<0.0001) and oxygen desaturation index (p<0.001) at week 26 and at the end of the study (week 51)
- A significant proportion of participants achieved a ≥50% reduction in AHI from baseline at week 26 (p<0.0001) and at week 51 (p<0.0001)
- AD109 improved OSA disease severity for 45.0% of participants at week 26 and 47.5% at week 51
- AD109 achieved OSA complete disease control (AHI<5) for 22.9% of participants at week 26 and 22.5% at week 51
Analysis of additional objective, subjective, and exploratory endpoints and safety data from the LunAIRo and SynAIRgy studies are ongoing and will be reported at a medical congress later this year.
“The consistency of the promising findings across both the LunAIRo and SynAIRgy trials provides robust clinical evidence that AD109 meaningfully improved sleep apnea severity and oxygenation,” says Sanjay Patel, MD, study chair for the LunAIRo clinical trial and director of UPMC Comprehensive Sleep Disorders Clinical Program, in a release.
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