AstraZeneca's Breztri Shows Significant Improvement in Uncontrolled Asthma Patients

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. 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). The comparator therapies included Symbicort (budesonide/formoterol fumarate or BFF, a standard therapeutic option), PT009 (BFF in an Aerosphere formulation) and the Symbicort and PT009 treatment groups combined.

In the pooled analysis of KALOS and LOGOS, Breztri also demonstrated clinically meaningful reductions in the annualized rate of severe asthma exacerbations versus ICS/LABA medicines in patients with or without a recent asthma exacerbation.

The primary investigator stated: "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."

The executive vice president of BioPharmaceuticals R&D at 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.

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). 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. The primary endpoints and treatment comparisons in the KALOS and LOGOS trials differed according to regulatory submission approaches.

In addition to the two registrational trials (KALOS and LOGOS), two qualifying trials, LITHOS and VATHOS, also met their primary endpoints. LITHOS and VATHOS included approximately 1,000 randomised patients.

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.

Asthma is a prevalent, chronic respiratory disease affecting as many as 262 million people worldwide, including over 25 million in the US. When uncontrolled, inflammation and muscle tightening in the airway (bronchoconstriction) may cause wheezing, breathlessness, chest tightness, coughing, and even death. 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. In the United States, national data indicates that approximately 39.4% of individuals with asthma experienced at least 1 asthma attack in 2021.