In Silico Lung Deposition Profiles of Three Single-Inhaler Triple Therapies in Patients with COPD Using Functional Respiratory Imaging

Dave Singh,1 Nicolas Roche,2,3 Libo Wu,4 Hosein Sadafi,5 Jan De Backer,6,7 Navid Monshi Tousi,5 Jonathan Marshall8 1Respiratory Research Group, University of Manchester, Medicines Evaluation Unit, Manchester University National Health Service Foundation Trust, Manchester, UK; 2Department of Respiratory Medicine, Hospital Cochin, APHP Centre, Paris, France; 3Université Paris Cité, Institut Cochin, U1016, Paris, France; 4Product Development Operations, AstraZeneca, Durham, NC, USA; 5Department of Computational Engineering, FLUIDDA NV, Kontich, Belgium; 6FLUIDDA NV, Kontich, Belgium; 7Department of Respiratory Medicine, University of Antwerp, Antwerp, Belgium; 8Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UKCorrespondence: Jonathan Marshall, Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CV2 0AA, UK, Tel +44 20 3749 5000, Email jonathan.marshall1@astrazeneca.comIntroduction: Inhalation is the foundational route for administering pharmacological treatments for chronic obstructive pulmonary disease (COPD). Given the relevance of both large and small airways in COPD, lung distribution deposition characteristics of different inhaler options could influence treatment effects. This study evaluated the total deposition of 3 single-inhaler triple therapies in the large and small airways.Methods: This study assessed lung deposition of different inhalers using in silico functional respiratory imaging from 20 patients with COPD. The first part evaluated budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) pressurized metered-dose inhaler (pMDI), beclomethasone dipropionate/glycopyrronium/formoterol fumarate dihydrate (BDP/G/F) pMDI, and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) dry powder inhaler (DPI) at 30 L/min. The second part assessed BGF pMDI and FF/UMEC/VI DPI at 60 L/min.Results: All 3 inhalers had different in silico total lung and large and small airways deposition profiles at 30 L/min, with BGF pMDI (54.8% to 57.7%) demonstrating a higher deposition profile across each therapeutic component versus BDP/G/F pMDI (38.6% to 40.5%) and FF/UMEC/VI DPI (24.0% to 36.1%), respectively. Similarly, at 60 L/min, the total deposition of all 3 components of BGF pMDI (57.2% to 58.5%) remained higher compared with FF/UMEC/VI DPI (19.8% to 34.1%).Conclusion: These findings provide quantitative insights into relative lung deposition distribution profiles and efficiency of delivery for 3 inhaler options. Further research is needed to understand if these deposition patterns could translate into real-world clinical effectiveness differences.Keywords: functional respiratory imaging, chronic obstructive pulmonary disease, small airways, single-inhaler triple therapy