Pooled KALOS/LOGOS Phase III readout: BREZTRI in uncontrolled asthma

A pre-specified pooled Phase III analysis across two trials in uncontrolled asthma reported that fixed-dose triple therapy with budesonide/glycopyrronium/formoterol improved lung function versus dual inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) comparators (Symbicort, PT009, and the combined Symbicort and PT009 groups), with statistically significant effects on FEV1 endpoints over 24 weeks.

The press release describes the pooled readout from KALOS and LOGOS and adds that regulatory filings for an asthma indication are under review in all major regions. It also reported statistically significant and clinically meaningful improvements in lung function with BREZTRI versus ICS/LABA comparators and stated that no new safety or tolerability signals were identified in KALOS or LOGOS.

The pooled analysis is described as including approximately 4,300 randomized patients across the replicate Phase III KALOS and LOGOS trials, comparing triple therapy against dual-combination ICS/LABA medicines and against the combined ICS/LABA comparator groups. The release lists two tested budesonide/glycopyrronium/formoterol doses—320/28.8/9.6 µg and 320/14.4/9.6 µg—and describes KALOS/LOGOS as randomized, double-blind, double-dummy, parallel-group, multicenter trials with variable length (24 to 52 weeks).

For lung-function reporting, it focuses on a 24-week timeframe for pooled endpoints and notes that primary endpoints included FEV1 AUC0–3 at Week 24 and trough FEV1 assessed over 12–24 weeks and over 24 weeks, with some treatment comparisons varying by submission approach.

For primary endpoints in the pooled KALOS/LOGOS analysis, the release reports that BREZTRI (budesonide/glycopyrronium/formoterol) improved morning pre-dose trough FEV1 by 76 mL versus the combined ICS/LABA comparator groups (95% CI, 57–94 mL; unadjusted p<0.001) over 24 weeks. Over the same timeframe, it also reports an improvement in FEV1 AUC0–3 of 90 mL versus the combined ICS/LABA comparators (95% CI, 72–108 mL; unadjusted p<0.001). The release characterizes these changes as “clinically meaningful,” without further detail in the summarized text on what the trough and AUC metrics imply for onset or duration of bronchodilation.

Beyond spirometry, the release states that the pooled KALOS/LOGOS analysis showed “clinically meaningful” reductions in the annualized rate of severe asthma exacerbations versus ICS/LABA medicines, including among patients with or without a recent asthma exacerbation.

On tolerability, the release stated that no new safety or tolerability signals were identified for BREZTRI in KALOS or LOGOS. It also states that regulatory filings for the triple therapy in asthma are under review in all major regions, summarizing the release’s reported efficacy, safety/tolerability, and submission status in a single pooled update.

Key Takeaways:

• A pooled analysis across KALOS/LOGOS was reported to show statistically significant improvements in trough FEV1 and FEV1 AUC0–3 versus combined ICS/LABA comparator groups over 24 weeks.
• The release stated that the pooled analysis showed reductions in the annualized rate of severe asthma exacerbations versus ICS/LABA medicines, without specifying the magnitude in the summarized text.
• The release stated that no new safety or tolerability signals were identified for BREZTRI in KALOS or LOGOS.
• Regulatory filings for an asthma indication were described as under review in all major regions.