AstraZeneca's BREZTRI Shows Significant Lung Function Improvements in Phase III Asthma Trials
Key Insights
BREZTRI Aerosphere demonstrated statistically significant improvements in lung function compared to dual-combination therapies in the Phase III KALOS and LOGOS trials, with 76mL and 90mL improvements in key respiratory measures.
The triple-combination inhaler showed clinically meaningful reductions in severe asthma (search) exacerbations across approximately 4,300 patients with uncontrolled asthma over 24-52 weeks.
Results published in The Lancet Respiratory Medicine support regulatory filings currently under review in major regions for BREZTRI's expansion from COPD (search) treatment to asthma (search) indication.
AstraZeneca's BREZTRI Aerosphere (budesonide/glycopyrronium/formoterol fumarate) has demonstrated statistically significant and clinically meaningful improvements in lung function for patients with uncontrolled asthma (search), according to full results from the Phase III KALOS and LOGOS trials published in The Lancet Respiratory Medicine. The triple-combination inhaler showed superior efficacy compared to standard dual-combination therapies in a pooled analysis of approximately 4,300 patients.
Trial Results Show Substantial Lung Function Gains
In the pre-specified pooled analysis of primary endpoints across both trials, BREZTRI improved lung function by 76mL (95% CI 57-94 mL, unadjusted p<0.001) as measured by morning pre-dose trough FEV1 over 24 weeks, and by 90mL (95% CI 72-108 mL, unadjusted p<0.001) as measured by FEV1 AUC0-3 over 24 weeks, compared to dual therapy combining ICS (search)/LABA (search) treatment groups.
The trials compared BREZTRI Aerosphere (320/28.8/9.6μg) against two fixed-dose, dual-combination therapies: Symbicort pressurised metered-dose inhaler and PT009 (BFF in an Aerosphere formulation). BREZTRI also demonstrated clinically meaningful reductions in the annualized rate of severe asthma (search) exacerbations versus ICS (search)/LABA (search) medicines in patients with or without a recent asthma exacerbation history.
Addressing Significant Unmet Medical Need
"Many of the 262 million people worldwide living with asthma (search) remain uncontrolled and still struggle with symptoms like frequent breathlessness, coughing and wheezing despite the use of dual maintenance therapy," said Alberto Papi, Professor and Chair of Respiratory Medicine at the University of Ferrara and primary investigator. "The KALOS and LOGOS trials show that the single fixed-dose triple therapy budesonide/glycopyrronium/formoterol, which combines the efficacy of an ICS (search), LAMA, and LABA (search), improved lung function, and, importantly, prevented future severe exacerbations in patients, regardless of exacerbation history."
The trials addressed a critical gap in asthma (search) care, as many patients remain uncontrolled despite standard of care medicines and continue to experience significant limitations on lung function and reduced quality of life.
Comprehensive Trial Design and Safety Profile
KALOS and LOGOS were replicate confirmatory, randomised, double-blind, double-dummy, parallel group, multi-centre trials with variable lengths of 24-to-52 weeks. The trial design was optimized to evaluate the 320/28.8/9.6μg dose of BGF, with primary efficacy endpoints including 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 measurements.
No new safety or tolerability signals were identified for BREZTRI in either trial. The drug's safety profile remains consistent with its established use in COPD (search) treatment, where it has been prescribed to more than 5.5 million patients globally in 2024.
Regulatory Progress and Market Expansion
BREZTRI is currently approved for chronic obstructive pulmonary disease (search) (COPD (search)) treatment in adults across more than 80 countries worldwide, including the US, EU, China, and Japan. Regulatory filings for BREZTRI in asthma (search) are currently under review in all major regions, supported by the positive results from KALOS and LOGOS, as well as two additional qualifying trials, LITHOS and VATHOS, which included approximately 1,000 randomised patients and also met their primary endpoints.
"With so many patients still experiencing the debilitating effects of uncontrolled asthma (search), we are excited about the potential for BREZTRI to improve lung function as well as prevent exacerbations in asthma," said Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca. "Building on its well-established profile in COPD (search), we hope to bring BREZTRI to patients with uncontrolled asthma as quickly as possible."
The single-inhaler, fixed-dose triple-combination combines formoterol fumarate (a LABA (search)), glycopyrronium bromide (a long-acting muscarinic antagonist), and budesonide (an ICS (search)), delivered via the Aerosphere pressurised metered-dose inhaler system.