Triple-Combination Therapy Met Primary End Point in Phase 3 Trials, Providing Treatment for Individuals With Asthma

A fixed-dose triple-combination therapy of budesonide, glycopyrronium, and formoterol fumarate (BGF, Breztri Aerosphere; AstraZeneca) met all primary end points in a phase 3 Kalos (NCT04609878) and Logos trial (NCT04609904) among individuals with uncontrolled asthma, demonstrating improvement in lung function compared with dual-combination inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) medicines.¹

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The inhaled triple-combination therapy is approved in over 80 countries, including the United States, the EU, China, and Japan, for the treatment of chronic obstructive pulmonary disease in adults.¹

Asthma is identified as one of the most common chronic respiratory diseases, impacting nearly 262 million individuals worldwide. The disease causes the airways to narrow and swell, making it difficult to breathe, known as bronchoconstriction. The severity of asthma differs between individuals, as some could experience frequent and major attacks that impact daily activities, while others experience minor attacks.^1,2

“Despite advancements in asthma treatments, millions of patients remain uncontrolled, which can cause frequent breathlessness, coughing, and wheezing, significantly impacting their ability to perform daily activities,” Alberto Papi, professor and chair of respiratory medicine at the University of Ferrara and director of the respiratory unit, cardiorespiratory department, S. Anna University Hospital, and primary investigator.¹

Asthma symptoms also vary among individuals, ranging from infrequent attacks to constant issues or those triggered by specific activities such as exercise. Common signs include shortness of breath, chest tightness or pain, wheezing, and sleep disturbances due to respiratory difficulties. Symptoms can also worsen with respiratory infections. Worsening asthma is characterized by more frequent and bothersome symptoms such as breathing difficulty and a greater need for a quick-relief inhaler. Additionally, certain triggers can cause flare-ups, such as exercise-induced asthma, occupational asthma, and allergy-induced asthma, according to Mayo Clinic.²

The Kalos and Logos trials were 2 large, replicated phase 3 studies that assessed the efficacy and safety of 2 doses of BGF (320/28.8/9.6 μg and 320/14.4/9.6 μg). These randomized, double-blind, double-dummy, parallel-group, multi-center trials spanned 24 to 52 weeks and compared BGF to 2 dual-combination therapies, budesonide and formoterol fumarate (PT009 and Symbicort pMDI).¹

A total of 4400 individuals were randomly assigned across both trials and evaluated the 320/28.8/9.6 dose of BGF, with primary efficacy end points measuring changes from baseline in forced expiratory volume in 1 second (FEV1), area under the curve from 0 to 3 hours at week 24, and trough FEV1 over 12 to 24 weeks and over 24 weeks.¹

The investigators reported no new safety or tolerability signals identified for BGF in the KALOS and LOGOS trials. However, the study authors noted that full results will be shared and presented at upcoming medical meetings.¹

“The results from the KALOS and LOGOS trials are exciting and demonstrate the potential of budesonide/glycopyrronium/formoterol to evolve the standard of care to more effectively treat asthma in a single inhaled triple therapy for patients who remain uncontrolled with dual maintenance therapy,” Papi said in a news release.¹

In addition to these 2 registrational trials, 2 qualifying trials, LITHOS (NCT05755906) and VATHOS (NCT05202262), which included around 1000 randomized patients, also successfully met their primary end points.¹

“We are excited by the positive results from the KALOS and LOGOS trials, which demonstrate that [BGF] could help improve the lives of the millions of patients living with asthma. These asthma data build on the well-established profile of [BGF] in COPD, and we look forward to sharing with regulatory authorities to bring this important medicine to a wider group of patients,” Sharon Barr, executive vice president of BioPharmaceuticals R&D, AstraZeneca, concluded in a news release.¹

REFERENCES

1. BREZTRI met primary endpoints in KALOS and LOGOS Phase III trials in asthma. AstraZeneca. News release. May 2, 2025. Accessed May 20, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/Breztri-met-primary-endpoints-in-kalos-and-logos-phase-III-trials-in-asthma.html

2. Asthma. Mayo Clinic. News release. March 8, 2025. Accessed May 20, 2025. https://www.mayoclinic.org/diseases-conditions/asthma/symptoms-causes/syc-20369653