Q&A: AD109 Shifts Focus in Obstructive Sleep Apnea Treatment Toward Symptom Improvement

As interest grows in pharmacologic approaches for obstructive sleep apnea (OSA), AD109 has emerged as a potential oral treatment option for patients who are unable or unwilling to use continuous positive airway pressure (CPAP) therapy. Positive findings from the phase 3 SynAIRgy and LunAIRo trials demonstrated improvements in OSA severity and patient-reported outcomes, supporting a recent New Drug Application submission to the FDA.

In an interview with Pharmacy Times, Sanjay R. Patel, MD, a primary investigator of LunAIRo and expert in sleep health, discusses the most clinically meaningful findings from the AD109 program, how the therapy could fit into the current treatment landscape, and what clinicians should consider as pharmacologic therapies for OSA continue to emerge.

Pharmacy Times: What do you consider the most clinically meaningful findings from the AD109 phase 3 program?

Sanjay R. Patel, MD: Because the main reason we treat obstructive sleep apnea is to improve symptoms, the most meaningful findings to me are the improvement in daytime fatigue and snoring. Although the improvements in fatigue overall were not substantial compared to placebo, in those patients who had baseline excessive daytime sleepiness, there were substantial improvements in fatigue seen with AD109 compared to placebo. Similarly, the snoring analysis suggested substantial improvements. These are two of the most common symptoms patients seek treatment for.

Pharmacy Times: How might an oral therapy such as AD109 fit into the current obstructive sleep apnea treatment landscape?

Patel: At this point, CPAP (or mandibular advancement devices) remain the first-line treatment options for patients with OSA. The SynAIRgy and LunAIRo trials were conducted in patients who either could not tolerate or refused to use CPAP. So I think it's clear that, with the current evidence, all patients with OSA who are interested in treatment should be counseled to give CPAP a try first and, in those who are good mandibular advancement device candidates, offer that as an option.

But for the sizable number of patients who try CPAP and mandibular advancement devices and cannot tolerate either, AD109 may be a viable treatment option to consider alongside tirzepatide and hypoglossal nerve stimulation. Based on current information, tirzepatide may be preferred in those with moderate to severe OSA and substantial obesity, hypoglossal nerve stimulation in those with moderate to severe OSA without substantial obesity, and AD109 in those without substantial obesity who do not want surgery or in those with milder-severity OSA but still with substantial symptom burden.

Pharmacy Times: What impact could approval of AD109 have for patients who struggle with CPAP adherence?

Patel: This drug may represent another option for those patients who have tried CPAP and, despite troubleshooting, cannot tolerate using CPAP, alongside other treatment options like mandibular advancement devices, hypoglossal nerve stimulation, and tirzepatide.

Pharmacy Times: What questions or considerations should clinicians keep in mind as they evaluate emerging pharmacologic approaches for obstructive sleep apnea?

Patel: I think it is very important to assess which symptoms are improved with emerging pharmacologic therapies, as well as which patients would be poor candidates for a particular treatment due to the side effect profile. Although the apnea-hypopnea index (AHI) plays a central role in defining who has OSA, this metric has never been validated as a therapeutic biomarker. As a result, it is much more important to know how various treatments address clinically meaningful endpoints like symptoms rather than focus solely on the change in AHI.