Full results from the positive Phase III KALOS and LOGOS trials published in The Lancet Respiratory Medicine showed AstraZeneca's Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate or BGF (320/28.8/9.6μg)) demonstrated statistically significant and clinically meaningful improvements in patients with uncontrolled asthma compared with dual-combination inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) medicines: Symbicort (budesonide/formoterol fumarate or BFF, a standard therapeutic option), PT009 (BFF in an Aerosphere formulation) and the Symbicort and PT009 treatment groups combined.1 Breztri is a single-inhaler, fixed-dose triple-combination of ICS/LABA and a long-acting muscarinic antagonist (LAMA).
In a pre-specified pooled analysis of the primary endpoints across the KALOS and LOGOS 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 90mL (95% CI 72-108 mL, unadjusted p<0.001, as measured by FEV1 AUC0-3 over 24 weeks) versus dual therapy (the ICS/LABA treatment groups combined).1
In the pooled analysis of KALOS and LOGOS, Breztri also demonstrated clinically meaningful reductions in the annualised rate of severe asthma exacerbations versus ICS/LABA medicines in patients with or without a recent asthma exacerbation. Full results can be found in The Lancet Respiratory Medicine.
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, Ferrara, Italy, and primary investigator, said: "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."
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "With so many patients still experiencing the debilitating effects of uncontrolled asthma, we are excited about the potential for Breztri to improve lung function as well as prevent exacerbations in asthma. Building on its well-established profile in COPD, we hope to bring Breztri to patients with uncontrolled asthma as quickly as possible."
There were no new safety or tolerability signals identified for Breztri in KALOS or LOGOS.
Breztri is an inhaled triple-combination therapy approved for the treatment of chronic obstructive pulmonary disease (COPD) in adults in more than 80 countries worldwide including the US, EU, China and Japan. Regulatory filings for Breztri in asthma are currently under review in all major regions.
Notes
Asthma
Asthma is a prevalent, chronic respiratory disease affecting as many as 262 million people worldwide,2 including over 25 million in the US.3 When uncontrolled, inflammation and muscle tightening in the airway (bronchoconstriction) may cause wheezing, breathlessness, chest tightness, coughing, and even death.2,4 Many patients remain uncontrolled despite the availability of standard of care medicines and continue to experience significant limitations on lung function and reduced quality of life.5,6
KALOS and LOGOS Phase III trials
KALOS and LOGOS were replicate confirmatory, randomised, double-blind, double-dummy, parallel group, multi-centre, 24-to-52-week variable length Phase III trials to assess the efficacy and safety of Breztri Aerosphere (320/28.8/9.6μg and 320/14.4/9.6μg) compared with two fixed-dose, dual-combination therapies of budesonide, an ICS, and formoterol fumarate, a LABA: Symbicort pressurised metered-dose inhaler (pMDI) and PT009 (in an Aerosphere formulation).1,7,8 KALOS and LOGOS included approximately 4,300 randomised patients.
The trial design was optimised to evaluate the 320/28.8/9.6μg dose of BGF. The primary efficacy endpoints for the two individual trials were the 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.1,7,8 The primary endpoints and treatment comparisons in the KALOS and LOGOS trials differed according to regulatory submission approaches. The full results published in The Lancet Respiratory Medicine report the pooled analysis of KALOS and LOGOS results for Breztri compared with the ICS/LABA treatment groups combined, and includes comparisons of Breztri to individual comparators arms measured across both trials in the supplement.
In addition to the two registrational trials (KALOS and LOGOS), two qualifying trials, LITHOS and VATHOS, also met their primary endpoints.9,10 LITHOS and VATHOS included approximately 1,000 randomised patients.
Breztri/Trixeo Aerosphere
Budesonide/glycopyrronium/formoterol fumarate (BGF), approved under the brand name Breztri Aerosphere in Japan, China and the US, and Trixeo Aerosphere in the EU, is a single-inhaler, fixed-dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a long-acting muscarinic antagonist (LAMA), with budesonide, an ICS, and delivered via the Aerosphere pMDI. Breztri/Trixeo Aerosphere (320/14.4/9.6μg) is approved to treat adults with COPD in more than 80 countries worldwide including the US, EU, China, Japan, and was prescribed to more than 5.5 million patients globally in 2024.11
AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals, is a key disease area and growth driver to the Company.
AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is 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.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide.
