Single-inhaler triple therapy with budesonide/glycopyrronium/formoterol fumarate (BGF) led to statistically significant and clinically meaningful improvements in lung function and reductions in severe exacerbations in patients with uncontrolled asthma. The findings from the recently published phase 3 KALOS and LOGOS trials demonstrate triple therapy’s ability to address a substantial unmet need among patients who remain symptomatic despite standard inhaled corticosteroid (ICS) and long-acting β₂-agonist (LABA) therapy.1
Even though guideline-recommended therapies are widely available, many patients experience persistent symptoms, impaired lung function, and recurrent exacerbations that negatively impact quality of life and health care utilization.2–3 The KALOS and LOGOS programs were designed to investigate whether the addition of a long-acting muscarinic antagonist (LAMA) to existing ICS-LABA therapy could deliver incremental clinical benefit in this population.
Commenting on the findings, the primary investigator, Alberto Papi, MD, FCCP, Professor of Respiratory Medicine at the University of Ferrara, Italy, highlighted the burden of uncontrolled asthma despite dual maintenance therapy and emphasized the importance of preventing future exacerbations in addition to improving lung function. He said the results also reinforce the growing body of evidence from other qualifying trials, including LITHOS and VATHOS, that similarly met their primary end points in patients with inadequately controlled asthma.4–5
KALOS and LOGOS were replicate, randomized, double-blind, double-dummy, parallel-group, multicenter trials enrolling approximately 4,300 patients with inadequately controlled asthma. Participants were randomized to receive BGF or one of two dual combination comparator therapies containing budesonide and formoterol (BFF). Treatment duration ranged from 24 to 52 weeks, depending on the study and end point assessed.
The primary efficacy end points included changes from baseline in FEV₁ measured as area under the curve from zero to three hours (AUC0-3) at week 24 and pre‑dose trough FEV1 at 12 to 24 weeks and more than 24 weeks. A prespecified pooled analysis across KALOS and LOGOS compared outcomes with BGF with the combined ICS-LABA treatment groups.
In the pooled analysis, BGF significantly improved lung function compared with dual therapy. Morning predose trough FEV1 increased by 76 mL (95% CI, 57-94 mL; unadjusted P < .001) at 24 weeks, while FEV1 AUC0-3 improved by 90 mL (95% CI, 72-108 mL; unadjusted P < .001). These gains exceeded thresholds generally considered clinically meaningful in asthma populations and were consistent across the two trials, the investigators noted.
Beyond lung function, BGF was associated with clinically meaningful reductions in the annualized rate of severe asthma exacerbations compared with ICS-LABA therapy. Importantly, the authors said this benefit was observed regardless of patients’ history of recent exacerbations, suggesting a broad protective effect in both higher- and lower-risk subgroups.
“The reductions in severe exacerbations reported in these two trials are significant and would certainly make a difference for patients with poorly controlled asthma,” said William B. Feldman, MD, PhD, MPH, Associate Professor of Medicine, David Geffen School of Medicine at UCLA, and a pulmonologist in the Divisions of Pulmonary, Critical Care & Sleep Medicine and Allergy & Immunology at UCLA Health. “The trials raise difficult questions about when we should be pulling the trigger for triple therapy in patients with poorly controlled asthma. Prior severe exacerbations do not seem to be a strict prerequisite.”
No new safety or tolerability signals were identified in KALOS or LOGOS. The safety profile of BGF was consistent with the known effects of its individual components. Investigators reported that adverse events aligned with prior experience in COPD, for which BGF is already approved in more than 80 countries worldwide.
Although not yet indicated for asthma, regulatory submissions are under review in major regions worldwide. Should regulatory approval be granted, triple therapy may represent an advance in the management of moderate to severe asthma by addressing airflow limitation and exacerbation risk in a single inhaler.
References
1. Papi A, Wise RA, Jackson DJ, et al. Budesonide–glycopyrronium–formoterol fumarate dihydrate in uncontrolled asthma (KALOS and LOGOS): twin multicentre, double-blind, double-dummy, parallel-group, randomised, phase 3 trials. Lancet Respir Med. 2026;14:350-362. doi:10.1016/S2213-2600(25)00457-6
2. Davis J, Trudo F, Siddall J, Small M. Burden of asthma among patients adherent to ICS/LABA: a real-world study. J Asthma. 2019;56(3):332-340. doi:10.1080/02770903.2018.1455858
3. Buhl R, Heaney LG, Loefroth E, et al. One-year follow up of asthmatic patients newly initiated on treatment with medium- or high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings. Respir Med. 2020;162:105859. doi:10.1016/j.rmed.2019.105859
4. A 12-week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler in Participants With Inadequately Controlled Asthma (LITHOS). ClinicalTrials.gov.
5. A 24-Week Efficacy and Safety Study to Assess Budesonide and Formoterol Fumarate Metered Dose Inhaler in Adult and Adolescent Participants With Inadequately Controlled Asthma (VATHOS). ClinicalTrials.gov.
