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

BACKGROUND: Inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy is a mainstay asthma treatment. LITHOS (clinicaltrials.gov identifier NCT05755906), a randomised phase 3 study, assessed efficacy and safety of low-dose budesonide/formoterol fumarate dihydrate (BFF) via a metered-dose inhaler (MDI) using Aerosphere co-suspension delivery technology (BFFA) versus low-dose budesonide via MDI using Aerosphere (BD). METHODS: Participants (aged 12-80 years; N=374) with inadequately controlled asthma (seven-item Asthma Control Questionnaire score ≥1.5) despite low-dose ICS or ICS/LABA were randomised to 12 weeks of twice-daily BFF 160/10 μg (BFFA 160) or BD 160 μg (BD 160). End-points included change from baseline in forced expiratory volume in 1 s (FEV1) area under the curve from 0-3 h (AUC0-3) (primary) and morning pre-dose trough FEV1 (key secondary) at week 12, onset of action, severe exacerbation rates and safety/tolerability. RESULTS: Least-square mean differences (95% CI) demonstrated that BFFA 160 provided superior lung function improvement versus BD 160 at week 12 for change from baseline in FEV1 AUC0-3 (200 (134-267) mL; p<0.0001) and morning pre-dose FEV1 (82 (20-144) mL; p=0.0096). Severe exacerbation rates were nominally reduced with BFFA 160 versus BD 160 (rate ratio (95% CI) 0.48 (0.23-0.97); unadjusted p=0.0419). No new or unexpected safety findings were observed; on-treatment adverse effects were comparable between treatments (BFFA 160, 18.4%; BD 160, 19.5%). CONCLUSION: These findings support the use of BFFA 160 twice daily with novel Aerosphere technology for the treatment of people aged 12-80 years with asthma inadequately controlled by low-dose ICS or ICS/LABA.