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

Background Inhaled corticosteroid (ICS)/long-acting β 2 -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 (BFF A ) 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 (BFF A 160) or BD 160 μg (BD 160). End-points included change from baseline in forced expiratory volume in 1 s (FEV 1 ) area under the curve from 0–3 h (AUC 0–3 ) (primary) and morning pre-dose trough FEV 1 (key secondary) at week 12, onset of action, severe exacerbation rates and safety/tolerability. Results Least-square mean differences (95% CI) demonstrated that BFF A 160 provided superior lung function improvement versus BD 160 at week 12 for change from baseline in FEV 1 AUC 0–3 (200 (134–267) mL; p<0.0001) and morning pre-dose FEV 1 (82 (20–144) mL; p=0.0096). Severe exacerbation rates were nominally reduced with BFF A 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 (BFF A 160, 18.4%; BD 160, 19.5%). Conclusion These findings support the use of BFF A 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.