In postmenopausal women, AD109 reduced AHI4 by 6.8 events\/hr versus 0.7 events\/hr with placebo, a geometric mean reduction of 59.6% versus 16%.\u00b9 Response rates for \u2265 50% and \u226570% AHI4 reduction were 47.2% and 29.7% with AD109, compared with 20.2% and 8.5% with placebo, respectively\u00b9 Hypoxic burden (HB4) fell by 69.8% with AD109 versus 20% with placebo.\u00b9<\/p>\n
In the non-menopausal cohort, AD109 reduced AHI4 by 5.3 events\/hr versus an increase of 0.7 events\/hr with placebo (geometric mean reduction, 44% vs 10.6%).\u00b9 Response rates for \u2265 50% and \u2265 70% reduction were 33% and 18.1% with AD109 versus 18.1% and 5.3% with placebo. HB4 declined by 50.9% with AD109 versus 12.9% with placebo.\u00b9<\/p>\n
AD109 Tolerability and Discontinuation by Menopausal StatusFrequently Asked Questions<\/p>\n
What is AD109?
AD109 is an investigational once-nightly oral combination of aroxybutynin, an antimuscarinic, and atomoxetine, a norepinephrine reuptake inhibitor. It is designed to target neuromuscular contributors to upper airway collapse during sleep.<\/p>\n
How did AD109 perform in postmenopausal women?
In this post hoc analysis, AD109 reduced AHI4 by a geometric mean of 59.6% and hypoxic burden by 69.8% in postmenopausal women. Both reductions were numerically greater than those in the non-menopausal cohort.<\/p>\n
Was AD109 tolerated differently in postmenopausal women?
Placebo-subtracted discontinuation due to adverse events was 17.7% in postmenopausal women and 17.5% in the non-menopausal cohort.<\/p>\n
Discontinuation of AD109 due to treatment-emergent adverse events was similar across subgroups, at a placebo-subtracted 17.7% in postmenopausal women and 17.5% in the non-menopausal cohort.\u00b9 In the published SynAIRgy trial, 21.2% of participants receiving AD109 and 3.1% receiving placebo discontinued therapy due to adverse events.\u00b2<\/p>\n
Mehra noted anticholinergic effects occurred more often among postmenopausal women but did not lead to more discontinuations in this group.<\/p>\n
\u201cDry mouth and constipation were more prevalent in the postmenopausal group compared to the non-postmenopausal group,\u201d Mehra said. \u201cThe discontinuation related to those symptoms was comparable between the two groups, so these symptoms weren\u2019t resulting in discontinuation of AD109 in the postmenopausal women.\u201d<\/p>\n
Investigators described the findings as hypothesis-generating. The analysis was exploratory and post hoc, comparisons between subgroups were descriptive, and age served as a partial proxy for menopausal status.\u00b9<\/p>\n
\u201cThis sets the stage for us to conduct additional analyses to look into this further,\u201d Mehra said.<\/p>\n
Apnimed reported in May 2026 it had submitted a New Drug Application (NDA) for AD109 to the FDA, and the agent has received Fast Track designation for OSA.\u2074<\/p>\n
Editor\u2019s note: Reported disclosures for Mehra include Amgen, JAZZ PHARMACEUTICALS, and VisionAir Solutions.<\/p>\n
References<\/p>\n
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; October 20, 2026; Phoenix, AZ.Strollo PJ Jr, Farkas R, Taranto-Montemurro L, Cronin J, Patel SR; SynAIRgy Investigators. Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnea: a randomized phase 3 trial (SynAIRgy). Am J Respir Crit Care Med. 2026;212(7):1569-1584. doi:10.1093\/ajrccm\/aamag215<\/a>AD109 effective as oral agent for obstructive sleep apnea, with Patrick John Strollo, MD. HCPLive. https:\/\/www.hcplive.com\/view\/ad109-effective-oral-agent-obstructive-sleep-apnea-patrick-john-strollo-md<\/a>. Published May 19, 2026. Accessed October 22, 2026.Apnimed. Apnimed announces publication of its phase 3 SynAIRgy trial of AD109 for obstructive sleep apnea in the American Journal of Respiratory and Critical Care Medicine. Published May 18, 2026. Accessed October 22, 2026. https:\/\/www.prnewswire.com\/news-releases\/apnimed-announces-publication-of-its-phase-3-synairgy-trial-of-ad109-for-obstructive-sleep-apnea-in-the-american-journal-of-respiratory-and-critical-care-medicine-302774259.html<\/a> <\/p>\n","protected":false},"excerpt":{"rendered":"In postmenopausal women, AD109 reduced AHI4 by 6.8 events\/hr versus 0.7 events\/hr with placebo, a geometric mean reduction…\n","protected":false},"author":2,"featured_media":638254,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[134,111,139,69],"class_list":["post-638253","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-new-zealand","tag-newzealand","tag-nz"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/638253","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=638253"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/638253\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/638254"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=638253"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=638253"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=638253"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}