BGF Triple Therapy Could Shift Asthma Treatment Landscape, With Alberto Papi, MD, PhD

AstraZeneca’s budesonide/glycopyrronium/formoterol fumarate (Breztri Aerosphere) significantly reduced severe exacerbations in patients with uncontrolled asthma, according to data from the phase 3 KALOS and LOGOS trials published in The Lancet Respiratory Medicine. According to investigators, these findings could influence how primary care clinicians escalate treatment when standard inhaled therapies fall short.^1,2

In the trials, the single-inhaler, fixed-dose triple therapy, which combines an inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta2-agonist (LABA), produced clinically meaningful reductions in annualized severe exacerbation rates compared with dual-combination regimens.

“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. 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” said Alberto Papi, primary investigator, professor and chair of respiratory medicine at the University of Ferrara, and director of the respiratory unit, Cardiorespiratory Department, S. Anna University Hospital in Ferrara, Italy.

In a pooled analysis of the 2 replicate Phase III trials, which included 4311 patients who received treatment, BGF demonstrated statistically significant improvements over dual-therapy (ICS/LABA) comparators. Key findings from the trials include:

• Improved Lung Function: Patients treated with BGF saw a 76mL (95% CI 57-94 mL, unadjusted p<0.001, as measured by morning pre-dose trough FEV1 over 24 weeks) improvement in lung function and a 90mL (95% CI 72-108 mL, unadjusted p<0.001, as measured by FEV1 AUC0-3 over 24 weeks) compared to those in dual therapy (the ICS/LABA treatment groups combined).

• Reduced Exacerbations: Triple therapy led to a meaningful reduction in the annualized rate of severe asthma exacerbations. BGF 28·8 versus BFF_A exacerbation rate ratio was 0·90 (95% CI 0·78–1·03; p=0·12). 627 (53·2%) adverse events were observed with BGF 28·8, 436 (60·0%) with BGF 14·4, 666 (55·2%) with BFF_A, and 698 (58·4%) with BFF_S.

• Consistent Safety Profile: The trials identified no new safety or tolerability signals for Breztri, building on its established profile in other respiratory conditions.

Asthma affects approximately 262 million people globally, including 25 million in the US alone. Primary care physicians often encounter patients who, despite adherence to dual-combination ICS/LABA maintenance therapy, continue to suffer from debilitating symptoms such as breathlessness, coughing, and wheezing.

Patient Care Online sat down with investigator Papi to learn more about how these trial results might impact management of asthma in primary care settings.

Primary Care’s Role in Effective Serve Ashma Treatment

Patient Care: How can clinicians really recognize when asthma is truly uncontrolled and requires that next step up to potentially BGF or another triple inhaler?

Alberto Papi, MD, PhD: There are very simple tools to be used to assess the level of control, 5 question, ACQ 5. But there are actually very simple items, including in recommendation, in general, recommendation to assess control, very simple, which are clinical in clinical practice, commonly checked by physician. How many times have you taken the rescue medication? How many times have you had symptoms, symptoms during the week and how was the night in terms of asthma syndrome? It's quite easy to assess the level of control. Besides being an expression of uncontrolled current condition, so the burden of the today disease being uncontrolled increase the risk of exacerbation. We get two types of information. One is that patient is uncontrolled, needs something to get a better control, thus a better quality of life. Second, we need to reduce the risk of exacerbation that is associated with an uncontrolled condition.

Patient Care: Persistent poor control, recurrent exacerbations really affect long term health and quality of life. Why is early intervention in patients that may require this step-up therapy so important?

Alberto Papi, MD, PhD: It is because we have to have a vision that is a bit long. While it is, it has to be, longer than just the acute event, which is an exhibition. Because beside being potentially very severe event, and it can happen also in patient with infrequent exacerbation in the past, beside the acute event and exacerbation impact heavily on the natural history of the disease. It increased the risk of future events. It increased the decline in lung function, the progressively can occur in this in these patients. So that's why the earlier the better, avoiding exacerbation is a way of maintaining a better level of lung function lifelong, and of reducing the risk of future events that are increasing the risk again of progression of the disease. It goes beyond the severity of the acute condition, but it impacts on the evolution of the disease.

Patient Care: Why is having a consistent effect, regardless of exacerbation history among patients important, especially in terms of clinician comfortability with prescribing an agent or advocating for use of an agent like this among their patients?

Alberto Papi, MD, PhD: We know from a number of epidemiological study that exacerbation are certainly the best predictor of future exacerbations. We know that when there is an exacerbation, patient is at risk of future events, but the concept is moving towards a stronger prevention concept. Why should we wait for one event to occur if we have already signs and the flag is already red, suggesting that there are there is risk of exacerbation, such as symptoms, uncontrolled asthma, low lung function, these are clear condition increasing the risk of exacerbations. And I think KALOS and LOGOS at the advantage of showing that in this population, even with low risk, usually consider of exacerbation. No exacerbation in the prior year, around 40% of the overall population and no exacerbation in the prior year can get the benefit of a reduced risk for exhibition. We cannot exclude the occurrence of exacerbation in asthmatic patient one of the of the most frequent triggers were probably the most frequent one, certainly in young in a young population, is infection, common infection, flu, influenza, and we cannot, unfortunately avoid totally the exposure. Having the airways well prepared to not respond in terms of worsening symptoms is clearly an advantage. The possibility KALOS and LOGOS was shown to have this protection, even in patient we no exacerbation in the prior year is novel, and it proposed possibility of avoiding even earlier, the chance to get acute events and the consequences, medium- and long-term consequence of the acute events.

Patient Care: For KALOS and LOGOS, you know this is not the first triple therapy trials that we've seen in phase 3. How clinically meaningful are the magnitude of differences that we're seeing, and how do these kind of stack up to prior phase three trials we've seen with a similar approach?

Alberto Papi, MD, PhD: We have already mentioned some important difference, such as the lack of need for prior exhibition to have an advantage in terms of reducing exhibition risk, which is unique in KALOS and LOGOS. But as you mentioned, none of the previous study that have evaluated the efficacy of a triple ICS/LABA in prevention exacerbation, managed to find a reduction in exacerbation in a conclusive way. There are a couple of study they get some preliminary results, but they are pulling together different doses, so it's not the proper way to assess. It cannot be considered conclusive. Or the comparison are with different groups. This is clean and neat. The results were prespecified. They were the primary pool analysis, and they're saying of the efficacy in the reduction. To be honest, there was a long time ago another study showing a reduction in exacerbation, but it was with 2 devices having not 1 triple therapy in one single device, but with two different devices. And we know the advantage in clinical practice, speaking to primary care physician of having a single device compared to device to take. Secondly, the population was limited to a subgroup of patient with persistent therefore limitation, which is just a proportion of the asthmatic patient population. So, it's the broader one, it's a single device, and the result, the results are neat and clear for the first time.

Note: The above transcript has been lightly edited for grammar and clarity.

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. Astrazeneca.com. Published February 13, 2026. Accessed February 18, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/positive-and-clinically-meaningful-results-from-the-phase-iii-kalos-and-logos-trials-for-breztri.html