Budesonide/formoterol fumarate dihydrate versus budesonide with a novel suspension technology for uncontrolled asthma: phase 3 VATHOS study.

BACKGROUND: Inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy is important in asthma. The phase 3 VATHOS study (ClinicalTrials.gov: NCT05202262) assessed the efficacy and safety of budesonide/formoterol fumarate dihydrate (BFF) via metered-dose inhaler (MDI) using Aerosphere co-suspension technology (BFFA) versus either budesonide (BD) via MDI using Aerosphere or BFF via dry-powder inhaler (BFFDPI). METHODS: Participants (age 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 (BFFA 160), BFF 320/10 μg (BFFA 320), BD 320 μg (BD 320) or open-label BFFDPI 320/9 μg, respectively. End-points included change from baseline in forced expiratory volume in 1 s area under the curve from 0 to 3 h (FEV1 AUC0-3) at 24 weeks (primary), and morning pre-dose trough FEV1 at 24 weeks, onset of action (day 1 change in FEV1, 5 min post-dose) and severe exacerbation rates (secondary). Adverse events (AEs) were recorded. RESULTS: BFFA 320 demonstrated superior lung function versus BD 320 at week 24 (mean change from baseline in FEV1 AUC0-3: 173 (95% CI 112-233) mL (p<0.0001); trough FEV1: 61 (95% CI 1-120) mL (p=0.0447); onset of action: 144 (95% CI 110-177) mL (p<0.0001)). Severe exacerbation rates were similar between BFFA 320 and BD 320 (rate ratio 1.02 (95% CI 0.61-1.70); p=0.9473). AEs were similar across treatments (BFFA 320, 50.3%; BFFA 160, 50.0%; BD 320, 38.1%; BFFDPI, 45.7%). BFFA 320 showed non-inferiority to BFFDPI in lung function. CONCLUSION: These findings support the use of BFFA 320 with co-suspension delivery technology in people with inadequately controlled asthma on medium-dose ICS or ICS/LABA.