Budesonide/formoterol fumarate dihydrate vs budesonide with a novel suspension technology for uncontrolled asthma: Phase 3 VATHOS study

Background Inhaled corticosteroid (ICS)/long-acting β 2 -agonist (LABA) therapy is important in asthma. Phase 3 VATHOS ( NCT05202262 ) assessed the efficacy and safety of budesonide/formoterol fumarate dihydrate (BFF) via metered-dose inhaler (MDI) using Aerosphere® co-suspension technology (BFF A ) versus either budesonide (BD) via MDI using Aerosphere® or BFF via dry-powder inhaler (BFF DPI ). Methods Participants (12–80 years; N=645) with inadequately controlled asthma on medium-dose ICS or ICS/LABA were randomised 1:2:2:2 to twice-daily BFF 160/10 μg (BFF A 160), BFF 320/10 μg (BFF A 320), BD 320 μg (BD 320) or open-label BFF DPI 320/9 μg, respectively. Endpoints included change from baseline in forced expiratory volume in one second area under the curve from 0–3 h (FEV 1 AUC 0–3 ) at 24 weeks (primary), and morning pre-dose trough FEV 1 at 24 weeks, onset of action (Day 1 change in FEV 1 , 5 min post-dose) and severe exacerbation rates (secondary). Adverse events (AEs) were recorded. Results BFF A 320 demonstrated superior lung function versus BD 320 at Week 24: mean (95% confidence interval [CI]) change from baseline in FEV 1 AUC 0–3 :173 (112, 233) mL (p<0.0001); trough FEV 1 : 61 (1, 120) mL (p=0.0447); onset of action: 144 (110, 177) mL (p<0.0001). Severe exacerbation rates were similar between BFF A 320 and BD 320 (rate ratio [95% CI], 1.02 [0.61, 1.70]; p=0.9473). AEs were similar across treatments (BFF A 320: 50.3%; BFF A 160: 50.0%; BD 320: 38.1%; BFF DPI : 45.7%). BFF A 320 showed non-inferiority to BFF DPI in lung function. Conclusion Findings support the use of BFF A 320 with co-suspension delivery technology in people with inadequately controlled asthma on medium-dose ICS or ICS/LABA.