BGF Triple Therapy Improves Lung Function in Phase 3 Uncontrolled Asthma Controls

Triple therapy with budesonide–glycopyrronium–formoterol fumarate (BGF) was associated with statistically significant improvements in lung function and reductions in severe exacerbations among patients with inadequately controlled asthma despite inhaled corticosteroid–long-acting β2-agonist (ICS–LABA) therapy, according to results from the phase 3 KALOS and LOGOS trials.1

Current Global Initiative for Asthma (GINA) recommendations support escalation to triple therapy with ICS–LABA–LAMA in patients with uncontrolled disease at step 5, particularly those with exacerbation risk.2 However, real-world uptake and optimal patient selection remain areas of ongoing investigation.

Alberto Papi, MD, from the University of Ferrara in Italy, Robert A. Wise, MD, from Johns Hopkins University, and colleagues conducted the KALOS and LOGOS trials: 2 multicenter, randomized, double-blind, double-dummy, parallel-group phase 3 studies enrolling patients aged 12 to 80 years with asthma inadequately controlled on medium- or high-dose ICS–LABA therapy.1 Participants were randomized to receive 1 of 4 regimens: BGF 320/28.8/10 μg, BGF 320/14.4/10 μg, budesonide–formoterol fumarate dihydrate via Aerosphere (BFFA), or budesonide–formoterol suspension (BFFS), administered twice daily for 24 to 52 weeks via a pressurized metered-dose inhaler.

A total of 8820 participants were recruited across both trials, with 4311 receiving treatments. The primary endpoints included changes from baseline in FEV₁ area under the curve over 0–3 hours (AUC₀–₃) and morning pre-dose trough forced expiratory volume in 1 second(FEV₁) over 24 weeks, as well as pooled annualized severe exacerbation rates.

Across the pooled analysis, BGF demonstrated superiority over dual therapy comparators in both FEV₁ measures and annualized exacerbation rates.1 These findings support the addition of a long-acting muscarinic antagonist (LAMA) in patients with persistent symptoms and may inform treatment escalation strategies.

BGF 320/28.8/10 μg met all multiplicity-adjusted primary endpoints. Compared with combined dual therapy comparators, BGF improved trough FEV₁ by 76 mL (95% CI, 57–94; P <.0001) and FEV₁ AUC₀–₃ by 90 mL (95% CI, 72–108; P <.0001). In pooled analyses, BGF reduced severe exacerbation rates versus combined budesonide–formoterol comparators (incidence rate ratio [IRR], 0.86; 95% CI, 0.76–0.97; P =.012) and versus BFFS alone (IRR, 0.82; 95% CI, 0.71–0.94; P =.0043). The reduction versus BFFA did not reach statistical significance (IRR, 0.90; 95% CI, 0.78–1.03; P =.12).1

Adverse events were reported in 53.2% of patients receiving BGF 28.8 μg, compared with 55.2% to 60.0% across comparator groups. No treatment-related deaths were reported, and the overall safety profile was consistent with known effects of ICS–LABA and LAMA therapies.1

The addition of a LAMA targets bronchoconstriction through muscarinic receptor antagonism, complementing the anti-inflammatory effects of ICS and bronchodilation from LABA. BGF combines budesonide (ICS), glycopyrronium (LAMA), and formoterol (LABA) in a pressurized metered-dose inhaler using co-suspension delivery technology. This formulation has previously been approved for chronic obstructive pulmonary disease (COPD) based on results from ETHOS and KRONOS.4,5 Its evaluation in asthma extends the potential role of this platform into a broader airway disease population.

Although statistically significant, the absolute improvements in FEV₁ were modest, and the clinical significance at the individual patient level may vary.1 The trials included a broad population, which enhances generalizability but may obscure subgroup-specific effects, such as by eosinophilic phenotype or biomarker status. Additionally, the lack of statistically significant exacerbation reduction versus one comparator (BFFA) highlights the need for further comparative effectiveness data.

“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,” the team 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. 2026;14(4):350-362. doi:10.1016/S2213-2600(25)00457-6

2. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2024 Update. Published 2022. Accessed on April 24, 2026. https://ginasthma.org/gina-reports/

3. Rabe KF, Martinez FJ, Ferguson GT, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020;383(1):35-48. doi:10.1056/NEJMoa1916046

4. Ferguson GT, Rabe KF, Martinez FJ, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Respir Med. 2018;6(10):747-758. doi:10.1016/S2213-2600(18)30327-8