AD109 Cuts AHI by 59.6% in Postmenopausal Women With OSA

Investigational aroxybutynin and atomoxetine (AD109) produced numerically greater reductions in airway obstruction and hypoxic burden in postmenopausal women with obstructive sleep apnea (OSA) than in non-menopausal participants, according to a post hoc analysis presented at CHEST 2026 in Phoenix.¹

OSA remains underdiagnosed in women, and risk rises after menopause as hormonal changes reduce upper airway stability. Postmenopausal women also tend to present with symptoms distinct from the classic sleepiness and snoring phenotype, which can delay recognition.

“Instead of sleepiness and snoring, they may have more fatigue,” said Reena Mehra, MD, MS, head of the Division of Pulmonary, Critical Care and Sleep Medicine at the University of Washington School of Medicine. “They may have more insomnia [and] depression.”

Mehra said these symptoms warrant further investigation in postmenopausal women to rule out OSA as a contributor. She attributed the elevated risk partly to declining estrogen and progesterone, which can drive endothelial, vascular, and ventilatory changes. Postmenopausal weight gain and its fat deposition pattern can also increase upper airway collapsibility.

AD109 Efficacy in Postmenopausal Women With OSA

The analysis drew on SynAIRgy, a 26-week trial, and LunAIRo, a 51-week trial.¹ Both were randomized, double-blind, placebo-controlled, parallel-arm phase 3 studies of AD109 in adults with mild to severe OSA who were intolerant of or refused positive airway pressure therapy.¹ Eligible participants had an apnea-hypopnea index of ≥ 5 events/hr using a 4% desaturation criterion (AHI4), a PROMIS-Fatigue raw score of ≥ 17, and, for women, a body mass index (BMI) of 18.5 to 42 kg/m².¹

Investigators classified women as postmenopausal based on menopause-related medical history or age ≥ 55 years. They compared this subgroup with a non-menopausal cohort of men and non-menopausal women.¹ Of 1,299 participants enrolled, 616 (47.4%) were women; 492 were postmenopausal (AD109, n = 262; placebo, n = 230) and 807 were non-menopausal (AD109, n = 391; placebo, n = 416).¹

Among postmenopausal women, the median AHI4 was 18.5 events/h, and 387 (78.7%) were having mild to moderate OSA.¹ At week 26, AD109 reduced AHI4 by 6.8 events/hr vs 0.7 events/hr with placebo, a geometric mean reduction of 59.6% vs 16.0%.¹ Response rates for ≥ 50% AHI4 reduction were 47.2% with AD109 vs 20.2% with placebo, and rates for at least a 70% reduction were 29.7% vs 8.5%.¹

Analyses were descriptive and used the on-treatment population, with missing data imputed by last observation carried forward. No P values were reported.¹

Hypoxic Burden and Safety of AD109 in Postmenopausal Women

AD109 reduced hypoxic burden (HB4) by 69.8% in postmenopausal women vs 20.0% with placebo.¹ In the non-menopausal cohort, AD109 reduced HB4 by 50.9% vs 12.9% with placebo.¹ AHI4 fell by 5.3 events/hr with AD109 in non-menopausal participants and rose by 0.7 events/hr with placebo, corresponding to geometric mean reductions of 44.0% vs 10.6%.¹

Response rates in the non-menopausal cohort were 33% for ≥ 50% AHI4 reduction and 18.1% for ≥ 70% reduction with AD109, compared with 18.1% and 5.3% with placebo.¹ Placebo-subtracted discontinuation due to treatment-emergent adverse events was similar across groups, at 17.7% among postmenopausal women and 17.5% in the non-menopausal cohort.¹

Mehra described hypoxic burden as the area under the desaturation curve associated with apneic and hypopneic events, capturing cumulative event-related hypoxia. Experimental data suggest intermittent hypoxia produces greater endothelial dysfunction through the nitric oxide pathway in women compared with men, she said.

“There may be sex-specific differences in how women versus men have this cardiovascular detriment in response to the hypoxia,” said Mehra. “We need to do more studies from a clinical standpoint to help corroborate some of these things we’re seeing experimentally.”

Mehra acknowledged several limitations, including the post hoc design, the absence of data on hormone replacement therapy, and the grouping of premenopausal women with men in the comparator cohort. She called for prospectively designed studies of risk stratification and treatment response in postmenopausal women for AD109 and other OSA therapies.

Apnimed’s new drug application for AD109 is under FDA review, with a Prescription Drug User Fee Act goal date of February 28, 2027.²

Watch part 1 here: AD109 Yields Numerically Greater OSA Improvements in Postmenopausal Women

Editor’s note: Reported disclosures for Mehra include Amgen, JAZZ PHARMACEUTICALS, and VisionAir Solutions.

References

1. Mehra R, Aurora RN, Lee-Iannotti JK, et al. Aroxybutynin and atomoxetine (AD109) in post-menopausal women with obstructive sleep apnea. Presented at: CHEST 2026 Annual Meeting; October 20, 2026; Phoenix, AZ.

2. Apnimed to present five abstracts, including two late breakers at CHEST 2026. Apnimed. Published October 12, 2026. Accessed October 26, 2026. https://www.financialcontent.com/article/gnwcq-2026-10-12-apnimed-to-present-five-abstracts-including-two-late-breakers-at-chest-2026