FDA Accepts NDA for Apnimed’s AD109 for the Treatment of Obstructive Sleep Apnea

The FDA has accepted for review the new drug application (NDA) for Apnimed’s AD109 (aroxybutynin 2.3 mg/atomoxetine 75 mg), an investigational once-nightly oral combination agent targeting the neuromuscular basis of upper airway collapse, for the treatment of adults with obstructive sleep apnea (OSA), with a PDUFA target action date of February 28, 2027.¹

"The FDA acceptance of our NDA is an important milestone for Apnimed as we advance toward our goal of expanding treatment options for people with OSA who continue to need more accessible solutions," Kevin Lind, chief executive officer at Apnimed, said in a statement.¹ "The NDA is supported by a clinical data package that reflects years of scientific innovation focused on a major unmet need. We believe AD109 has the potential to offer an important new treatment option for adults with OSA, if approved, and we look forward to engaging with the FDA during its review."

The NDA is supported by data from 2 positive phase 3 randomized, double-blind, placebo-controlled trials, dubbed SynAIRgy (NCT05813275) and LunAIRo (NCT05811247), which both met their primary end point compared with placebo among adults with mild-to-severe OSA. Designed for use across varying levels of disease severity, AD109 offers the promise of a safe, effective, and more user-friendly alternative to current OSA treatments, which are often invasive or difficult for patients to tolerate.

The Phase SynAIRgy Trial

SynAIRgy was a randomized, double-blind, placebo-controlled, 26-week study evaluating AD109, a fixed-dose oral combination of aroxybutynin 2.5 mg and atomoxetine 75 mg, in adults with mild-to-severe OSA who had failed or declined positive airway pressure (PAP) therapy.² The study enrolled 646 participants across 69 centers in the United States and Canada, including a diverse patient population reflective of real-world sleep clinic populations. Participants were nearly evenly split by sex, with 49.3% women, and included broad representation across body mass index (BMI) classes and OSA severity ranges.

At baseline, the median apnea-hypopnea index (AHI) was 19.6 events per hour, with 35% of participants classified as mild OSA, 42% moderate, and 23% severe. Overall, the study met its primary endpoint, showing statistically significant improvements in AHI at week 26. In the intent-to-treat analysis, AD109 achieved a model-estimated 44.1% reduction in AHI from baseline compared with a 17.6% reduction for placebo (P <.0001), corresponding to an estimated treatment difference of –4.0 events/hour (95% CI, –6.4 to –1.6; P = .001).1

Across SynAIRgy, AD109 was generally well tolerated, though adverse event (AE)–related discontinuations were more common with active treatment than placebo. Overall, 21.2% of participants receiving AD109 discontinued therapy because of AEs compared with 3.1% in the placebo arm. The most common AEs included dry mouth, insomnia, nausea, and urinary hesitation, most of which were mild and occurred early after treatment initiation. In SynAIRgy, no treatment-related serious adverse events or deaths were reported.

The Phase 3 LunAIRo Trial

LunAIRo, a randomized, double-blind, placebo-controlled trial, comprised 660 adults with OSA who were intolerant of or refused continuous PAP therapy. Spanning 64 centers, participants were randomly assigned to either AD109 (n = 329) or placebo (n = 331) and instructed to take their assigned treatment once daily before bedtime.³

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In LunAIRo, treatment with the AD109 led to significant reductions in AHI, the primary end point, relative to those on placebo. At the 26-week mark, patients on the therapy achieved a mean reduction in AHI of 46.8% compared with reductions of 6.8% for placebo, which was statistically significant (P <.001). Notably, these effects were maintained until the end of the study, around week 51 (P <.001).

Throughout the study, AD109-treated patients demonstrated meaningful improvements in oxygenation, a secondary end point, as assessed by reductions in hypoxic burden (P <.0001) and oxygen desaturation index (P <.001) at week 26 and end of study (week 51). In addition, a significant proportion of patients achieved at least 50% reduction in AHI from baseline at week 26 (P <.0001) and at week 51 (P <.0001).

Treatment with AD109, a first-in-class anti-apneic neuromuscular modulator, led to improved OSA disease severity for 45.0% of participants at week 26 and 47.5% by week 51. Complete disease control, defined as an AHI of fewer than 5 events per hour, was achieved in 22.9% of AD109-treated patients at week 26 and 22.5% at week 51.

In the data update, AD109 was considered well tolerated, with the most common treatment-emergent AEs being mild or moderate in severity and consistent with previous studies. Notably, no serious AEs in the study were attributed to AD109.

The Phase 2 MARIPOSA trial

In the previously conducted phase 2 MARIPOSA trial (NCT05071612), AD109 demonstrated significant therapeutic benefits in a 211-patient cohort randomized to AD109, atomoxetine, or placebo. Treatment with AD109 (2.5 mg/75 mg) reduced the median AHI from 20.5 to 10.8 events/hour, a statistically significant improvement compared with placebo (P <.001).⁴

Among those who completed MARIPOSA, 41% achieved an AHI below 10, 44% had a reduction greater than 50% from baseline, and 15% saw reductions of 80% or more. AD109 also improved daytime functioning, as measured by PROMIS-Fatigue (P <.05), and showed favorable trends in sleep impairment and disturbance scores. In contrast, atomoxetine alone worsened nighttime sleep quality and failed to improve daytime OSA symptoms, reinforcing the value of AD109 as a more comprehensive treatment approach.

REFERENCES
1. Apnimed Announces FDA Acceptance of New Drug Application for AD109, An Investigational Oral Pill to Treat Adults with Obstructive Sleep Apnea (OSA). News release. July 14, 2026. Accessed July 15, 2026. https://apnimed.com/article/apnimed-announces-fda-acceptance-of-new-drug-application-for-ad109-an-investigational-oral-pill-to-treat-adults-with-obstructive-sleep-apnea/
2. 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. News release. Apnimed. May 19, 2025. Accessed July 15, 2026. https://apnimed.com/article/ad109phase3toplineresults/
3. Apnimed reports positive topline results from second phase 3 trial of AD109, reinforcing potential of first oral pill for obstructive sleep apnea. News release. July 23, 2025. Accessed July 15, 2026. https://apnimed.com/article/ad109toplinephase3results/
4. Apnimed presented positive phase 2b results on AD109, an investigational oral drug for obstructive sleep apnea, for the first time at ATS 2023. News release. Apnimed. May 21, 2023. Accessed July 15, 2026. https://apnimed.com/article/apnimed-presented-positive-phase-2b-results-on-ad109-an-investigational-oral-drug-for-obstructive-sleep-apnea-for-the-first-time-at-ats-2023/