Apnimed shared data from a proof-of-concept study exploring two potential oral therapeutic candidates for the treatment of patients with obstructive sleep apnea (OSA), AD504 (atomoxetine + trazodone) and AD182 (atomoxetine + an orexin antagonist), during an oral presentation at SLEEP 2022.

“This study reinforces the potential of AD504 as a follow on to our lead product AD109,” says Larry Miller, MD, Apnimed CEO, in a release. “We believe that exploring multiple oral drug combinations and subpopulations could uncover powerful new treatment options for people with OSA. We’re pleased that these data continue to reinforce the study of AD504, which is currently included alongside our lead candidate AD109 in our phase 2b MARIPOSA study.”

This was a proof-of-concept, randomized, controlled, double-blind, single-dose, three-period crossover study of 15 patients who met eligibility criteria. Each patient received one night of AD504 (atomoxetine and trazodone), one night of AD182 (atomoxetine and an orexin antagonist), and one night of placebo. Doses were given immediately prior to bedtime.

AD504 showed a significant reduction of the apnea hypopnea index (AHI) (from 18.2 [11.8 to 31.3] on placebo to 7.4 [5.4 to 16.1] events/h on AD504, p=0.024 and hypoxic burden (HB) from 46.3 [25.1 to 88.3] on placebo to 18.7 [14.9 to 43.5], p=0.003 on AD504. AD182 also demonstrated a trend towards reduction in hypoxic burden relative to placebo but the effects were smaller than what was seen for AD504. Both combination drugs also demonstrated a favorable safety profile.

An investigational, oral pharmacologic combination dosed once daily at bedtime, AD504 may be beneficial for OSA patients who also experience sleep disturbance. AD504 is Apnimed’s second core program and is a combination of atomoxetine and trazodone. Further Phase 2 development of AD504 has been incorporated in the MARIPOSA study (a large Phase 2 study assessing both AD109 and AD504, clinicaltrials.gov identifier NCT05071612). Apnimed is developing proprietary formulations of the AD504 combination.

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