Despite hopes that BAY2253651 would fill the void of pharmacological agents for obstructive sleep apnea, the SANDMAN trial (ClinicalTrials.gov Identifier: NCT03603678) found that BAY2253651 had no apparent therapeutic effect in treating OSA, though it was safe and well-tolerated. Although the SANDMAN trial sponsor terminated the trial for futility, a chemically-altered follow-up compound is about to be studied. These were among the findings of research recently published in the European Respiratory Journal.
Currently, there are no pharmacological options available for the treatment of OSA. BAY2253651, which was developed based on an animal model, targets genioglossus muscle activation by amplifying upper airway reflex activity. The SANDMAN trial was the first-in-patient randomized, multi-center, double-blind, parallel group-comparison study to investigate the efficacy and safety of BAY2253651 for the treatment of OSA.
The study included 34 adults being treated for OSA with continuous positive airway pressure (CPAP) (for 3 months or more). Participants all had an apnea-hypopnea-index (AHI) of 15-50/hour after 48 hours of CPAP withdrawal, documented by polysomnography (PSG), and at least 4 hours of sleep time participated. In the first part of the study, participants were randomized to either 100 µg BAY2253651 intranasally or placebo nose spray and then went to sleep. The second part of the study was an open-label follow-up in which 100 µg BAY2253651 was applied at home over 5 consecutive nights, with data collected via home pulse oximetry.
The researchers found that although BAY2253651 was safe and well-tolerated in the treated group of OSA patients, the responder rate was 1 (6.3%) for BAY2253651 and 1 (6.7%) for placebo and there were no differences in any of the standard PSG parameters (all P >.05).
Limitations of the trial were the small sample size and missing data on actual drug delivery. In conclusion, investigators noted, “While an effect on polysomnographic parameters of OSA can be ruled out with confidence (based on part A and B data), the trial was non-informative from a mechanistic point of view. A proof of mechanism trial with a chemically altered follow-up compound is currently recruiting patients (NCT04236440).”
Disclosure: This research was supported by Bayer. Please see the original reference for a full list of disclosures.
Gaisl T, Turnbull CD, Weimann G, et al. BAY 2253651 for the treatment of obstructive sleep apnea: a multi-centre, double-blind, randomized controlled trial (SANDMAN). Eur Respir J. Published online September 16, 2021. doi:10.1183/13993003.01937-2021