Triple Inhaler Improves Outcomes in Uncontrolled Asthma Trials

Key Takeaways

• Higher-dose BGF was associated with improved lung function across comparisons and lower severe exacerbation rates versus BFFcombined and BFFS.
• The studies were multicentre, randomized, double-blind, double-dummy phase 3 trials in patients aged 12-80 years with asthma uncontrolled despite daily medium- or high-dose ICS-LABA.
• Adverse-event rates were broadly similar across groups, and no deaths were treatment related.

In pooled KALOS and LOGOS phase 3 trials, BGF 320/28.8/10 μg was associated with about 14% fewer severe exacerbations than combined budesonide-formoterol comparators in adolescents and adults with uncontrolled asthma despite daily medium- or high-dose ICS-LABA. All prespecified multiplicity-adjusted primary endpoints were met across the completed studies. The comparison evaluated fixed-dose triple therapy against budesonide-formoterol regimens in this population.

KALOS and LOGOS were multicentre, randomized, double-blind, double-dummy, parallel-group phase 3 studies at 378 sites in 20 countries and 324 sites in 15 countries. Participants aged 12-80 years had asthma that remained inadequately controlled despite daily medium-dose or high-dose ICS-LABA. Randomization was 1:1:1:1 to BGF 320/28.8/10 μg, BGF 320/14.4/10 μg, BFFA 320/10 μg, or BFFS 320/9 μg, all twice daily by pressurised metered-dose inhaler. Comparators included budesonide-formoterol delivered with Aerosphere co-suspension technology and the current suspension formulation. Treatment lasted 24-52 weeks, depending on regional health authority guidance, and the trial design prespecified lung function and pooled exacerbation analyses.

Primary lung function endpoints were change from baseline in morning pre-dose trough FEV1 and FEV1 AUC0-3 from day 1 to week 24. The pooled primary analysis across both studies assessed annualised severe exacerbations. Versus BFFcombined, BGF 28.8 improved trough FEV1 by 76 mL, with a 95% CI of 57-94 and p<0.0001. The FEV1 AUC0-3 difference was 90 mL, with a 95% CI of 72-108 and p<0.0001. Least-squares mean differences favored BGF 28.8 across all comparisons, and all multiplicity-adjusted primary endpoints were met.

In pooled analyses, the annualised severe exacerbation incidence rate ratio for BGF 28.8 was 0.86 versus BFFcombined, with a 95% CI of 0.76-0.97 and p=0.012. The corresponding ratio was 0.82 versus BFFS, with a 95% CI of 0.71-0.94 and p=0.0043. Against BFFA, the rate ratio was 0.90, with a 95% CI of 0.78-1.03 and p=0.12, which did not show a statistically significant difference. Overall, severe exacerbation rates were lower versus BFFcombined and BFFS, with no statistically significant difference versus BFFA.

Across both studies, 8820 participants were recruited, and 4311 received treatment across the four study groups. Those treated included 1179 in BGF 28.8, 726 in BGF 14.4, 1210 in BFFA, and 1196 in BFFS. Adverse events occurred in 53.2% of BGF 28.8 recipients and 60.0% of BGF 14.4 recipients. Rates were 55.2% with BFFA and 58.4% with BFFS, and no deaths were treatment related. The safety profile was broadly similar across study groups.