NeuroVoices: Sanjay R. Patel, MD, MS, on Advances in Pharmaceutical Treatment for Sleep Apnea

Sanjay R. Patel, MD, MS

(Credit: University of Pittsburgh)

There are no currently approved pharmacologic treatments available for patients with obstructive sleep apnea (OSA). Apnimed’s AD109, a first-in-class once-daily investigational medication, aims to be the first oral pharmacologic therapy for patients OSA by targeting key neurological pathways that activate upper airway dilator muscles to maintain an open airway during sleep. Recently, at the 2024 SLEEP Annual Meeting, held June 1-5, in Houston, Texas, an outline was presented of the company’s phase 3 SynAIRgy trial (NCT05813275), a randomized, controlled study assessing the efficacy and safety of the agent as a potential treatment for OSA.¹

The ongoing study includes about 640 patients with OSA who are randomly assigned 1:1 to either AD109 or placebo for a 26-week treatment period. The trial includes adults who either decline or are unable to tolerate continuous positive airway pressure (CPAP) therapy, the standard of care for OSA. In addition, eligible participants are those who have an apnea-hypopnea index (AHI)-4 (4%)(desaturation definition for hypopneas) more than 5 and a body mass index less than 42 kg/m2 for women and less than 40 kg/m2 for men. In the trial, the primary end point is response rate of AD109 compared with placebo, defined as at least a 50% reduction in AHI4 over the 26-week period using a polysomnogram.

In more recent news, the company announced early completion of enrollment for their LunAIRo phase 3 trial (NCT05811247), an additional study assessing AD109 in patients with OSA.² In a new iteration of NeuroVoices, primary investigator of LunAIRo Sanjay R. Patel, MD, MS, professor of medicine, epidemiology, & clinical and translational science at University of Pittsburgh, sat down to further discuss the main components of AD109 being tested in the LunAIRo study. Patel, who also serves as the director of the Center for Sleep and Cardiovascular Outcomes Research and medical director of the UPMC Comprehensive Sleep Disorders Program, talked about the potential benefits of treatment over traditional CPAP therapy for patients with sleep apnea.

NeurologyLive: Discuss your experience with SLEEP 2024; were there any trends that you thought were notable?

Sanjay R. Patel, MD, MS: It's a really exciting time in sleep medicine. There's been a lot of interest and development of potentially novel pharmaceutical targets in sleep medicine for a range of sleep disorders, particularly for sleep apnea, which is the focus of my research interests.

What are the details about this phase 3 trial investigating AD109 in sleep apnea?

As probably your audience knows, sleep apnea is a really common condition, one of the most common sleep disorders in the United States. The incidence is growing because of the obesity epidemic. The first line treatment for sleep apnea has traditionally been CPAP which works really well but is not very well tolerated. In general, patients are not excited to start CPAP, and a large number of them cannot tolerate CPAP. There's been a lot of interest in developing alternative treatments. A lot of patients have been interested in finding a pharmaceutical treatment for their sleep apnea.

This study, the LunAIRo study, is designed to evaluate a novel pharmacologic treatment AD109 which is a combination drug that combines atomoxetine and R-oxybutynin for the purpose of evaluating its efficacy as a treatment for sleep apnea. These 2 drugs were selected because they could potentially increase neurologic output for the upper airway dilator muscles and thereby open up patency of the throat. Oxybutynin is norepinephrine reuptake inhibitor that has been believed to increase neural tone during nonREM sleep. R-oxybutynin is an anticholinergic that perhaps minimizes the suppression of neuromuscular tone during REM sleep.

In earlier phase 2 studies, the combination of these drugs were shown to lead to a 47% reduction in the AHI, a measure of sleep apnea severity over the short term, as well as lead to an improvement in fatigue scores. The LunAIRo study is a phase 3 trial to evaluate this drug over a longer term, to see if it can be used as an alternative treatment for sleep apnea. In terms of the design of the study, it is a randomized control, double blinded trial, placebo controlled with 2 parallel arms. Patients either get randomized to the active drug or to a placebo in a 1:1 fashion. They're then followed for 52 weeks to evaluate the efficacy of the drug. The drug is slowly tapered up, there's a 1 week run in dose where they're taking a lower dose of AD109 and then if they tolerate it well, go up to the full dose.

Along the way, there are a number of overnight sleep studies done at baseline, at 13 weeks, at 26 weeks, and then at the end of the year to evaluate the primary outcome which is whether or not the patient has a 50% reduction in the AHI. There are also a number of secondary outcomes, looking at a range of patient symptoms related to sleep apnea, and then a number of other outcomes like sleep architecture and the hypoxemic burden, as well as safety outcomes that are going to be assessed as well.

Is there anything else you wanted to add regarding the unmet needs among patients with sleep apnea?

Again, existing data suggests that up to 50% of patients with sleep apnea cannot or will not tolerate CPAP in the long term. There's a huge unmet need for all of these patients with sleep apnea, and there's a range of different treatment options being developed. AD109 is one of them that really is targeting neuromuscular function. There has beenexciting data in the phase 2 short term studies and we've already very quickly filled enrollment for the phase 3 trial with 660 patients, which I think is just a testament of how many patients out there are interested in a pharmacologic treatment like this. We're hopeful that we'll get the results out there in about a year from now and, fingers crossed, there's some promising results that give patients another treatment option.

Transcript edited for clarity. Click here to view more NeuroVoices.

REFERENCES
1. Strollo P, Taranto-Montemurro L. Aroxybutynin and Atomoxetine for the Treatment of OSA: Rationale and Design of the SYNAIRGY Phase 3 RCT. Presented at: 2024 SLEEP Annual Meeting; June 1-5; Houston, TX. ABSTRACT 0546.
2. Apnimed Announces Completion of Enrollment in Phase 3 LunAIRo Study of AD109, the Potential First Nighttime Oral Treatment for Obstructive Sleep Apnea. News Release. Published May 9, 2024. Accessed June 12, 2024. https://apnimed.com/completion-of-phase-3-enrollment-lunairo-study-ad109-osa/