UroMarker Test Panel for Obstructive Sleep Apnea

PROJECT SUMMARY PGXL Technologies is developing a patented, non-invasive urine-based assay for obstructive sleep apnea (OSA) in children. OSA occurs in up to 3% of children and as much as 10% of the pediatric orthodontic population. OSA can lead to disturbed sleep, neurobehavioral problems, neurocognitive impairments, and hypertension in children. Diagnosis is primarily limited to in-clinic sleep studies because patient history and physical examinations are not adequately able to differentiate OSA from primary snoring (PS), i.e., snoring without associated sleep apnea or underlying sleep disorder. Polysomnography (PSG) tests are the gold standard for diagnosis, but they are highly expensive, require an overnight stay in a supervised sleep clinic, are difficult for children, and do not meet the need for screening OSA. There are several home sleep tests (HSTs) that have been cleared for use in children that use similar sensors and methods as PSG studies in the home, but the Academy of Sleep Medicine currently does not recommend the use of HSTs for diagnosis of OSA in children due to the lack of physician supervision and a lack of sufficient evidence of efficacy. There is an unmet need for a rapid and sensitive test for OSA that can be used for potential diagnosis, patient monitoring as they undergo treatment, and screening of broader populations. PGXL Technologies is advancing development of a urine-based, multiplexed immunoassay for screening children for OSA. The four biomarkers urocortin-3 (UCN3), kallikrein-1, orosomucoid-1, and uromodulin are present in urine and have previously shown high sensitivity and specificity for detection of OSA in children using ELISA assays. Prior to this project, PGXL has adapted two of the four biomarkers to the Meso Scale Discovery (MSD) platform, a clinical diagnostic platform based on a highly sensitive electrochemiluminescent detection approach. PGXL has demonstrated initial clinically relevant detection for two biomarkers, and acquired a retrospective set of pediatric urine samples that can be used to determine reference ranges. The goal of this Fast-Track proposal will be to advance development through initial clinical validation. In Phase I, of this Fast-Track project, PGXL will integrate immunoassays for the remaining biomarkers and optimize the analytical range for each of the assays in the UroMarker panel using pediatric urine specimens. In Phase II, PGXL will complete analytical validation required to meet CLIA requirements and conduct a prospective study to establish clinical cutoffs for an algorithm that includes all four biomarkers. PGXL will also develop a prototype urine collection kit that can be used for urine collection at home and mailed to a CLIA lab for analysis. Success with these goals will also inform a larger multi-site clinical study that is expected in Phase IIb and will support FDA clearance of the test. These milestones provide a path toward the commercial deployment of a high-throughput, multiplex test for rapid OSA screening through simple home-based sample collection to improve patient outcomes.