AstraZeneca announced positive high-level results from its Phase III KALOS and LOGOS trials evaluating Breztri Aerosphere in patients with uncontrolled asthma. The fixed-dose triple-combination therapy met all primary endpoints, showing statistically significant and clinically meaningful improvement in lung function compared to standard dual-combination inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) treatments.
The trials involved approximately 4,400 randomized patients and tested Breztri Aerosphere, which contains budesonide (an inhaled corticosteroid), glycopyrronium (a long-acting muscarinic antagonist), and formoterol fumarate (a long-acting beta2-agonist) at a dose of 320/28.8/9.6μg.
Addressing a Significant Unmet Need
Asthma affects an estimated 262 million people worldwide, with nearly half of those treated with dual therapy remaining uncontrolled. This lack of control significantly limits lung function and decreases quality of life for millions of patients who experience symptoms like breathlessness, coughing, and wheezing.
Professor Alberto Papi, primary investigator and Chair of Respiratory Medicine at the University of Ferrara, emphasized the importance of these findings: "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. 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."
Trial Design and Endpoints
KALOS and LOGOS were replicate, randomized, double-blind trials designed to investigate Breztri as a potential treatment for asthma. The primary efficacy endpoints included change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24 and trough FEV1 over 12-24 weeks and over 24 weeks.
In addition to these two registrational trials, two qualifying trials, LITHOS and VATHOS, which included approximately 1,000 randomized patients, also met their primary endpoints.
Safety Profile
No new safety or tolerability signals were identified for Breztri in either the KALOS or LOGOS trials, which is consistent with its established safety profile in COPD treatment.
Potential Impact on Treatment Landscape
Sharon Barr, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, expressed optimism about the results: "We are excited by the positive results from the KALOS and LOGOS trials, which demonstrate that Breztri could help improve the lives of the millions of patients living with asthma. These asthma data build on the well-established profile of Breztri in COPD, and we look forward to sharing with regulatory authorities to bring this important medicine to a wider group of patients."
Current Approval Status
Breztri is currently approved as an inhaled triple-combination therapy for the treatment of chronic obstructive pulmonary disease (COPD) in adults in more than 80 countries worldwide, including the US, EU, China, and Japan. According to AstraZeneca, the medication was prescribed to more than 5.5 million patients globally in 2024.
Next Steps
AstraZeneca plans to share the full results from the two Phase III trials with regulatory authorities and present them at an upcoming medical meeting. If approved for asthma, Breztri would expand its indication beyond COPD, potentially benefiting millions of additional patients worldwide who struggle with uncontrolled asthma despite current treatment options.
The positive results from these trials align with AstraZeneca's stated ambition to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks, and achieve clinical remission in immune-mediated diseases.
