Budesonide–Glycopyrronium–Formoterol Found to Reduce Severe Exacerbations in Uncontrolled Asthma

New twin phase 3 trials suggest that single-inhaler triple therapy with budesonide–glycopyrronium–formoterol fumarate dihydrate improved lung function and reduced severe exacerbations in persons with asthma inadequately controlled despite medium- or high-dose inhaled corticosteroid–long-acting β₂-agonist therapy.¹

Findings come from the multicenter studies, KALOS and LOGOS, which were published online February 12, 2026, in the The Lancet Respiratory Medicine.¹

“Many of the 262 million people worldwide living with asthma remain uncontrolled and still struggle with symptoms like frequent breathlessness, coughing and wheezing despite the use of dual maintenance therapy,” Alberto Papi, MD, PhD, professor and chair of respiratory medicine at the University of Ferrara, Ferrara, Italy, and primary investigator, said in a press release.² “The KALOS and LOGOS trials show that the single fixed-dose triple therapy budesonide/glycopyrronium/formoterol, which combines the efficacy of an ICS, LAMA, and LABA, improved lung function, and, importantly, prevented future severe exacerbations in patients, regardless of exacerbation history.”

The studies were randomized, double-blind, double-dummy, parallel-group trials conducted across 378 sites in 20 countries (KALOS) and 324 sites in 15 countries (LOGOS). Participants were aged 12 to 80 years and had inadequately controlled asthma despite daily medium- or high-dose inhaled corticosteroid–long-acting β₂-agonist (ICS–LABA) use.¹

Participants were randomly assigned (1:1:1:1) to receive twice-daily treatment via pressurized metered-dose inhaler for 24 to 52 weeks: budesonide 320 μg, glycopyrronium 28.8 μg, and formoterol 10 μg (BGF 28.8); budesonide 320 μg, glycopyrronium 14.4 μg, and formoterol 10 μg (BGF 14.4); budesonide–formoterol fumarate dihydrate using Aerosphere co-suspension delivery technology (BFFA) 320 μg, 10 μg; or budesonide–formoterol fumarate dihydrate suspension formulation (BFFS; Symbicort) 320 μg, 9 μg.¹

The primary lung function end points were change from baseline in forced expiratory volume in 1 second (FEV₁) area under the curve from 0 to 3 hours (AUC₀–3) and change from baseline in morning pre-dose trough FEV₁ from day 1 to week 24, assessed over 24 weeks depending on regional regulatory guidance. The primary pooled analysis across both trials evaluated annualized severe exacerbation rates.¹

Between December 15, 2020, and March 21, 2025 (KALOS), and March 1, 2021, and March 20, 2025 (LOGOS), 8820 participants were recruited and 4311 received treatment. Of these, 1179 received BGF 28.8, 726 received BGF 14.4, 1210 received BFFA, and 1196 received BFFS.¹

In each study, all prespecified multiplicity-adjusted primary end points for regulatory comparisons were met. Least squares mean differences favored BGF 28.8 for change from baseline in trough FEV₁ and FEV₁ AUC₀–3 across all comparisons (all P < .05). Compared with combined budesonide–formoterol comparators (BFF_combined), least squares mean differences over 24 weeks for BGF 28.8 were 76 mL (95% CI, 57–94; P < .0001) for morning pre-dose trough FEV₁ and 90 mL (95% CI, 72–108; P < .0001) for FEV₁ AUC₀–3.¹

In addition, BGF 28.8 reduced severe exacerbation rates compared with BFF_combined (incidence rate ratio [IRR], 0.86; 95% CI, 0.76–0.97; P = .012) and compared with BFFS (IRR, 0.82; 95% CI, 0.71–0.94; P = .0043). The exacerbation rate ratio for BGF 28.8 versus BFFA was 0.90 (95% CI, 0.78–1.03; P = .12).¹

Adverse events were reported in 627 participants (53.2%) receiving BGF 28.8, 436 (60.0%) receiving BGF 14.4, 666 (55.2%) receiving BFFA, and 698 (58.4%) receiving BFFS. No deaths were considered treatment related.¹

The investigators concluded that budesonide–glycopyrronium–formoterol improved lung function and reduced severe exacerbation rates in a broad population of patients with asthma inadequately controlled despite medium- or high-dose ICS–LABA therapy. These effects were observed regardless of recent exacerbation history.¹

“Given that these findings were observed regardless of recent exacerbation history, BGF could benefit individuals with inadequately controlled asthma without requiring a recent episode of acute deterioration on ICS–LABA before escalation,” Papi and colleagues wrote.¹

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. Published online February 12, 2026. doi:10.1016/S2213-2600(25)00457-6
2. Positive and clinically meaningful results from the Phase III KALOS and LOGOS trials for BREZTRI in patients with uncontrolled asthma published in The Lancet Respiratory Medicine. News release. AstraZeneca. February 13, 2026. Accessed February 13, 2026. https://www.astrazeneca-us.com/media/press-releases/2026/Positive-and-clinically-meaningful-results-from-the-Phase-III-KALOS-and-LOGOS-trials-for-BREZTRI-in-patients-with-uncontrolled-asthma-published-in-The-Lancet-Respiratory-Medicine.html