Shots: 

• Cardiopulmonary events associated with COPD are responsible for an increasing mortality rate in COPD patients. ETHOS trial, a posthoc analysis navigates BGF’s impact on a wide range of cardiopulmonary outcomes beyond COPD exacerbations 

• The post-hoc analysis reveals that AstraZeneca’s Breztri led to a 20% reduction in the risk of severe cardiopulmonary events. AstraZeneca is currently working to find proactive treatment to address cardiopulmonary risk and reduce mortality in COPD with the Tharros trial 

• Today, at PharmaShots we have Robert Fogel, VP of Global Medical Affairs, R&I, AstraZeneca, and Dave Singh Professor of Clinical Pharmacology and Respiratory Medicine at the University of Manchester, UK, sharing insights from the ETHOS trial 

Saurabh: A post-hoc analysis of the ETHOS trial explored BGF’s impact on a broader range of cardiopulmonary outcomes beyond COPD exacerbations. Can you elaborate on the rationale behind this approach and its significance for COPD management?  

Robert: COPD impacts more than 391 million people globally and kills more people than lung cancer and breast cancer combined. With no substantial improvement in mortality over the past two decades, COPD continues to be under-prioritised, underfunded and undertreated.  As a leading cause of death and disability, more needs to be done to address COPD.  

The lungs and heart are fundamentally linked and work together. COPD mechanisms elevate the risk of both lung and heart events, including severe or even fatal COPD exacerbations and cardiac events. This elevated risk of both pulmonary and cardiac events in COPD patients is called cardiopulmonary risk.   

Cardiopulmonary causes are among the most common reasons for death in patients with COPD.  

And in some countries, COPD is the second most common cause of emergency room visits. Further, only 50% of patients with COPD are alive within 3.6 years of their first hospitalisation for a severe exacerbation.   

AstraZeneca has a bold ambition to eliminate COPD as a leading cause of death. By fundamentally shifting the treatment paradigm to a more proactive approach, we can improve prognosis in COPD for the millions of people affected, helping them live healthier, longer and more active lives.  

Saurabh: Specifically, BGF 320 demonstrated a decrease in the risk of severe cardiopulmonary events versus LAMA/LABA. Can you elaborate on these results and what it means within the context of the larger Breztri clinical programme?  

Dave: In the ETHOS post-hoc analysis of cardiopulmonary outcomes, Breztri was associated with a 20% reduction in risk of severe cardiopulmonary events compared to the dual bronchodilator LAMA/LABA in patients with moderate-to-very-severe COPD and a history of recent exacerbations.  

Previous analysis of ETHOS and KRONOS from Breztri’s Phase III clinical trial programme showed that Breztri demonstrates reductions in traditional endpoints, such as moderate or severe exacerbations.   

The new post-hoc analysis highlights how Breztri is associated with reducing a broader range of cardiopulmonary outcomes.   

Taken together, the results can help transform treatment goals in COPD.  

Saurabh: Moving forward, what are the most crucial areas for additional research on BGF treatment for COPD patients?  

Robert: Evidence from trials such as ETHOS demonstrate the need for proactive treatment to address cardiopulmonary risk and reduce mortality in COPD; however, there is still a need for additional evidence to advance scientific understanding in this area and improve outcomes for patients.  

AstraZeneca recently announced the initiation of THARROS, a first of-its-kind, landmark Phase III trial investigating the potential of Breztri to reduce the risk of cardiopulmonary outcomes, including death from respiratory and cardiac causes, in patients with COPD.   

We have also initiated the ATHLOS Phase III trial assessing the impact of Breztri on integrated cardiopulmonary parameters associated with health status and survival in patients with COPD.  

With THARROS and ATHLOS, AstraZeneca aims to demonstrate the potential of triple therapy to improve cardiopulmonary outcomes. This is part of our ambition to eliminate COPD as a leading cause of death by continuing to expand the scientific understanding of COPD and how to treat to prevent exacerbations.    

But while we continue to expand our scientific understanding of COPD, what we do to help patients today is equally important.   

We must start to take a preventative approach – and specifically one that prioritises prompt therapeutic interventions to improve outcomes. By fundamentally shifting the treatment paradigm to a more proactive approach, we can improve prognosis in COPD for the millions of people affected, helping them live healthier, longer and more active lives.  

Saurabh: In real-world clinical practice, what factors would guide a physician’s decision to incorporate BGF into a patient’s COPD treatment regimen?  

Dave: COPD management has historically been reactive with pharmacotherapy not escalated until symptoms worsen. But it should be addressed and treated with a similar sense of urgency as that given to other chronic illnesses like cardiovascular diseases or lung cancer.  

Today, there is a growing body of scientific evidence and momentum in the clinical community towards a more proactive approach to COPD paired with earlier intervention to address cardiopulmonary risk, prevent exacerbations, and, ultimately, lower the risk of premature death.    

In fact, the 2024 GOLD report highlighted this, as well as the treatment effect of some fixed-dose triple combination therapies on mortality. The report also highlights the proactive therapeutic approach needed to improve outcomes in COPD.  

Robert: It is essential that even newly diagnosed COPD patients are considered at risk of pulmonary and cardiac events.   

For that reason, we must prioritise prompt and early therapeutic intervention to prevent exacerbations, lower cardiopulmonary risk, and reduce mortality. 

Image Source: Canva 

About the Authors: 

Robert Fogel 

After graduating from Columbia University, College of Physicians and Surgeons in 1993, Robert B Fogel MD spent the next 11 years expanding both his academic and professional portfolios at Massachusetts General Hospital, Brigham and Women’s Hospital and Harvard Medical School.  

Robert has been working within the pharmaceutical industry since 2004 gaining extensive knowledge and experience in medical affairs, clinical development, and commercial areas at local, regional, and global levels. He has proven to be an exceptional Strategic Medical Affairs and Clinical Research Leader with accomplishments in therapeutic area strategy, portfolio management, clinical research, drug development, CRO oversight and Global Medical Affairs.  

Robert currently holds the position of Vice President of Global Medical Affairs, Respiratory and Immunology at AstraZeneca in Gaithersburg, Maryland. Here, he is responsible for the leadership of AZ’s Medical Affairs strategy and planning, along with the development and execution of key Practice Change Initiatives within Respiratory and Immunology. Whilst partnering closely with both global and local cross functional teams, Robert also acts as a senior external scientific leader maintaining strong relationships with medical experts and stakeholder groups including societies and health care systems.  

To date, Robert has co-authored 66 original articles and numerous reviews, book chapters, editorials, and clinical communications. 

Dave Singh 

Dave Singh is Professor of Clinical Pharmacology and Respiratory Medicine at the University of Manchester, UK. He graduated in medicine from Cambridge University and then specialised in clinical pharmacology and respiratory medicine. His research interest is the development of new drugs for asthma and COPD. He is the medical director of the Medicines Evaluation Unit, where he has acted as principal investigator in over 400 clinical trials. He is a member of the GOLD Science Committee. He was previously the chair of the European Respiratory Society airway pharmacology group. He is currently an editor of the European Respiratory Journal and European Respiratory Review. He is a fellow of the European Respiratory Society and of the British Pharmacology Society. He has over 450 publications. 

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