Abstract Rationale KALOS and LOGOS, twin Phase 3, double-blind, double-dummy, randomized studies, compared fixed-dose triple combination inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA)/long-acting muscarinic antagonist (budesonide/glycopyrrolate/formoterol fumarate), delivered via a metered-dose inhaler using Aerosphere™ co-suspension delivery technology (BGF), with ICS/LABA (budesonide/formoterol fumarate), either as the standard suspension formulation (Symbicort®; BFFS) or using Aerosphere™ co-suspension delivery technology (BFFA). KALOS and LOGOS demonstrated the superiority of BGF 36 (320/36/9.6 µg) for improving lung function and exacerbation rates versus combined comparator groups BFFA and BFFS (BFFCombined) in participants with inadequately controlled asthma. This analysis assessed the effect of BGF 36 versus ICS/LABA comparators on patient-reported outcomes (PROs), onset of action and onset of effect in pooled KALOS and LOGOS. Methods Participants (≥12 y) with inadequately-controlled asthma despite ICS/LABA use were randomized (pooled N = 4311) to BGF 36, BGF 18 (320/18/9.6 µg), BFFA (320/9.6 µg), or BFFS (320/9 µg) twice daily for 24-52 weeks. Secondary and exploratory endpoints included asthma-related PROs by percentage of responders for ACQ-5 and ACQ-7 (≥0.5 unit decrease from baseline), AQLQ+12 (≥0.5 unit increase from baseline), SGRQ (≥4.0 unit decrease from baseline), onset of action (change in FEV1 at 5-minutes post-dose on Day 1) and onset of effect (measured in a participant subgroup via the onset of effect questionnaire OEQ to ascertain whether they could feel their study medication working). Results High percentage of responders were observed across all treatment arms over 24 weeks in ACQ-5 (BGF 36: 72.7%, BFFA: 71.2%, BFFS: 68.6%), ACQ-7 (BGF 36: 70.0%, BFFA: 66.4%, BFFS: 64.2%), AQLQ+12 (BGF 36: 58.2%, BFFA: 58.4%, BFFS: 54.5%) and SGRQ (BGF 36: 72.6%, BFFA: 70.7%, BFFS: 69.2%). Fast onset of action with improvements 100mL from baseline at 5-minutes was observed across all groups (Table). A high percentage of participants experienced a fast onset of effect as evaluated by the OEQ (BGF 36: 56/76 73.7%, BFFA: 53/83 63.9%, BFFS: 41/70 58.6%). Despite a similar proportion across the groups demonstrating a change in FEV1 of 100mL at 5-minutes, the numerically larger OEQ improvement in the BGF 36 group was supported by a post-hoc analysis showing a larger change in FEV1 at 5-minutes post-dose compared to BFFA, BFFS, and BFFCombined (Table). Conclusions BGF 36 shows symptomatic benefits and faster onset of action, with greater improvements compared with BFF. This fast onset is likely predominantly driven by formoterol, with additional benefit with the addition of glycopyrrolate, highlighting the benefits of this treatment in uncontrolled asthma. This abstract is funded by: AstraZeneca
Patel et al. (Fri,) studied this question.