Shots:
- AstraZeneca is exploring the potential of Breztri Aerosphere in uncontrolled asthma, aiming to address the large proportion of patients who remain symptomatic on standard dual therapy and improve lung function and quality of life.
- Findings from the KALOS and LOGOS Phase III trials revealed meaningful lung function gains and a 14% reduction in severe exacerbations versus dual ICS/LABA therapy, highlighting the promise of triple therapy for harder-to-control patients.
- PharmaShots welcomes Caterina Brindicci of AstraZeneca for an engaging dialogue on Breztri’s clinical potential and the evolving strategy to advance next-generation respiratory care.
Saurabh: Breztri has been primarily indicated for COPD. What led AstraZeneca to investigate its potential in uncontrolled asthma, and which unmet needs in this patient population were you aiming to address?
Caterina: Our decision to investigate Breztri’s potential in uncontrolled asthma was driven by the ongoing unmet clinical need for this population.
Asthma affects more than 262 million patients worldwide, and in some markets, approximately half of patients treated with dual therapy remain uncontrolled, even when adherent to treatment, which can significantly limit lung function and decrease quality of life. This patient population needs and deserves more options.
Breztri can help address this need. Breztri combines three medicines in one inhaler, which helps to reduce the inflammation and swelling in the airways, relax the muscles around the airways and prevent the airways from tightening.
With the data from the Phase III KALOS and LOGOs trials published in The Lancet Respiratory Medicine, we are confident in the potential of Breztri in asthma and are focused on unlocking its full potential in this indication to transform care in a broad population of patients, regardless of recent exacerbation history.
Building on its established profile in COPD, the results from our KALOS and LOGOS trials establish Breztri as a fixed-dose triple-therapy that delivers protection from exacerbations in COPD and in asthma regardless of recent exacerbation history.
The trial design was optimised to evaluate the 320/28.8/9.6μg dose of Breztri, which differs from the approved dose to treat adults with COPD (320/14.4/9.6μg).
Saurabh: The KALOS and LOGOS studies demonstrated statistically significant improvements in lung function, including trough FEV₁ and AUC₀–3. Clinically, how meaningful are these improvements for patients and physicians in everyday practice?
Caterina: In each of the replicate trials, Breztri demonstrated statistically significant improvements in lung function (p<0.05) as measured by FEV1 AUC0-3 and morning pre-dose trough FEV1 versus the individual comparators, Symbicort, PT009, and the treatment groups combined.
Breztri also demonstrated a statistically significant reduction in the pooled rate of severe exacerbations compared with the ICS/LABA treatment groups combined. There were variations in the reduction of severe exacerbations against the individual comparators.
More specifically:
- In a 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 versus combined ICS/LABA treatment groups.
- In a pooled analysis of the primary endpoints across the KALOS and LOGOS trials, Breztri improved lung function by 90mL (95% CI 72-108 mL, unadjusted p<0.001) as measured by FEV1 AUC0-3 over 24 weeks versus combined ICS/LABA treatment groups.
- Breztri demonstrated a statistically significant 14% reduction in the pooled rate of severe exacerbations compared with the ICS/LABA treatment groups combined.
- Breztri showed a fast onset of action, with 74% of patients feeling the effects and retaining 170mLs within five minutes on day one.
Saurabh: Could you elaborate on the rationale for selecting dual ICS/LABA therapy as the comparator? Why was this considered the most appropriate benchmark for evaluating Breztri in this setting?
Caterina: Currently, ICS/LABA is the standard of care for patients with uncontrolled asthma. However, a significant number of patients still remain uncontrolled on this treatment regimen, even when adherent to treatment.
While other inhalers combine two medicines (ICS/LABA), Breztri combines three medicines in one inhaler (ICS/LABA/LAMA). By combining the efficacy of three medicines in one inhaler, it helps to reduce the inflammation and swelling in the airways, relax the muscles around the airways and prevent the airways from tightening.
The results from KALOS and LOGOS show that Breztri demonstrated statistically significant and clinically meaningful improvements compared with dual-combination ICS/LABA medicines in patients with uncontrolled asthma.
Saurabh: The trials showed consistent reductions in severe exacerbations across patient subgroups. How might these findings influence treatment decisions earlier in the asthma care pathway?
Caterina: These trial results show that Breztri, as a fixed-dose triple therapy with the efficacy of the ICS, LAMA and LABA combined, can meaningfully improve lung function and reduce the risk of severe exacerbations. This is especially important for those whose symptoms aren’t well-controlled with dual-therapy, ICS/LABA inhalers.
These findings indicate that patients, regardless of their recent exacerbation history, may benefit from moving treatment from dual-therapy options to Breztri, a triple therapy. Patients should always discuss potential treatment options with their healthcare provider.
Saurabh: Given the heterogeneity of uncontrolled asthma, how do the observed safety and tolerability outcomes support the overall interpretation of Breztri’s efficacy?
Caterina: We did not identify any new safety concerns with Breztri in the KALOS and LOGOS trials compared to current standard treatments.
For scale, The KALOS and LOGOS trial recruited approximately 4300 participants with inadequately controlled asthma from 378 sites in 20 countries (KALOS), and 324 sites in 15 countries (LOGOS).
Saurabh: With regulatory submissions ongoing worldwide, what are AstraZeneca’s expectations for Breztri’s approval in asthma, and how might it shape existing treatment guidelines?
Caterina: We are very excited about these results and look forward to bringing these benefits to people with uncontrolled asthma as quickly as possible.
Saurabh: Has AstraZeneca begun exploring the potential health economic impact of Breztri, such as translating reduced exacerbations into cost savings for healthcare systems?
Caterina: AstraZeneca is at the forefront of making respiratory care more sustainable for the health of both patients and the environment.
Health-care systems face significant challenges in dealing with respiratory diseases. In the process of providing essential care for patients, they also contribute to greenhouse gas emissions through doctor and hospital visits, as well as medicine use. The less controlled a patient’s disease is, the higher their use of health-care resources.
Saurabh: Finally, how do the KALOS and LOGOS findings inform AstraZeneca’s broader respiratory R&D strategy, particularly in addressing asthma-COPD overlap?
Caterina: Beyond Breztri, we are on a mission to eliminate asthma attacks and achieve clinical remission through multiple avenues:
- Reinforcing our anti-inflammatory reliever inhaled portfolio as the backbone of care
- Driving towards clinical remission with biologics
- Introducing novel oral and inhaled medicines to help people who are not controlled on standard of care inhaled therapies but will not have access to biologics.
About Caterina Brindicci
Senior Vice President & Global Head Research and Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca
As Senior Vice President & Global Head Research and Development, Respiratory & Immunology, Caterina Brindicci works end-to-end from pre-clinical discovery research through to Phase III, regulatory submission, approval, and subsequently into life cycle management. Caterina leads a global team of +900 inspirational scientists, clinicians, biometrics experts, and regulatory affairs specialists.
Caterina is a Respiratory Physician, holding a PhD in clinical pharmacology and molecular biology from Imperial College London and an MBA from Bocconi University.
Caterina plays a pivotal role in AstraZeneca’s BioPharmaceuticals R&D Leadership Team and holds +15 years of experience in senior roles across the pharmaceutical industry. Prior to joining industry, Caterina worked as a Pulmonologist at the National Heart & Lung Institute and Royal Brompton Hospital.
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