Atomoxetine/Aroxybutynin Reduced Nighttime Airway Obstruction and Improved Daytime Impairment in Individuals with Obstructive Sleep Apnea
In the phase 2 MARIPOSA study (NCT05071612), individuals treated with atomoxetine/aroxybutynin (AD109; Apnimed, Cambridge MA) for obstructive sleep apnea (OSA) showed a reduction in nighttime airway obstruction and an improvement in daytime cognitive function.
The Apnea-Hypopnea Index (AHI) was reduced from a median of 20.5 to 10.8 events/hour in the atomoxetine/aroxybutynin 75 mg/2.5 mg dose arm and reduced from 19.4 to 9.5 events/hour in the atomoxetine/aroxybutynin 75 mg/5 mg dose arm. During the study, there was a statistically significant reduction in the AHI for both doses (P<.001 vs placebo). Almost half (41%) of participants (n=294) who completed the study achieved an AHI below 10 when treated with atomoxetine/aroxybutynin, 44% had more than 50% in reduction from baseline, and 15% of treated participants had an 80% or more reduction. The AHI reduction occurred the entire night compared with standard care therapies used for part of the night.
On the Epworth Sleepiness Scale (ESS), a 5-point decrease in median ESS over 1-month from 12 to 7 was observed with atomoxetine 75 mg/aroxybutynin 2.5 mg compared with a 2-point decrease observed for placebo.
“MARIPOSA results support the therapeutic potential of AD109 as a convenient, nightly treatment for OSA, which would represent a major breakthrough in the management of this serious disease,” said Paula Schweitzer, PhD, an investigator in the MARIPOSA trial and the director of Research at St. Luke’s Sleep Medicine and Research Center, Chesterfield, MO. “Improved nighttime breathing and sleep, and improved daytime fatigue were observed, which have the potential to dramatically improve quality of life.”
Ron Farkas, MD, PhD, chief medical officer of Apnimed added, “MARIPOSA was a large study that we believe provides compelling evidence, along with earlier Apnimed studies, of AD109’s potential to improve the lives of people with OSA. We plan to request an end of phase 2 meeting with FDA shortly to obtain further clarity on phase 3 and our subsequent marketing application for AD109.”
The MARIPOSA study was a randomized double-blind placebo-controlled of 1-month duration. Participants had a wide range of OSA severity (AHI 4 of 10-45). Participants were randomized to parallel arms comparing 2 doses of atomoxetine/aroxybutynin, 2 doses of a second candidate in an earlier phase of development, atomoxetine alone, and placebo. Participants treated with atomoxetine/aroxybutynin who were studied in prior trials (atomoxetine 75 mg/aroxybutynin 2.5 mg) saw a large and statistically significant (P<0.001) reduction in AHI4 at 1-month vs placebo.
The most common adverse events in participants treated with atomoxetine/aroxybutynin were dry mouth, insomnia, and nausea with no new or unexpected adverse events.