Shots: 

• At ESC 2024, AstraZeneca presented insights from the real-world OverTTuRe study, exploring the challenges of early diagnosis in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) 

• Mina Makar, SVP and Commercial Lead of the Global Cardiovascular, Renal, and Metabolism (CVRM) Biopharmaceuticals Business Unit at AstraZeneca, shared real-world insights on how ATTR-CM manifests as cardiac symptoms 

• Mina highlighted the potential of AstraZeneca’s approved therapy, Wainua (eplontersen), for treating hereditary transthyretin-mediated amyloidosis and its ongoing evaluation for ATTR-CM, with data readout expected in 2026. 

Saurabh: What are some of the main challenges in diagnosing ATTR amyloidosis early, and how can we overcome them, given that the study highlights the lengthy process many patients face?   

Mina: Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) is a systemic, progressive and ultimately fatal condition that can lead to heart failure (HF) within several years of onset. One of the primary challenges in diagnosing ATTR-CM early is that its signs and symptoms often overlap with more common conditions, such as heart failure with preserved ejection fraction (HFpEF). As a result, ATTR-CM frequently goes undetected or is misdiagnosed, delaying appropriate treatment.     

Our data presented at ESC further highlighted the lengthy diagnostic journey many patients face despite guidelines and expert recommendations for diagnosing and managing ATTR-CM. To overcome these challenges, we need to raise awareness among healthcare providers, improve diagnostic tools such as imaging and biomarker tests, and ensure timely access to specialist care.     

Saurabh: The OverTTuRe study gathered data from 2017 to 2022. During that time, did you notice any changes or trends in patient demographics or how the disease manifests?   

Mina: The OverTTuRe study provided real-world insights into how ATTR manifests, particularly in relation to cardiac symptoms. One of the most significant findings was that cardiac manifestations, including heart failure, were recorded up to 5 years before an ATTR diagnosis. This indicates that many patients may have been presenting with early signs of ATTR-CM without being accurately diagnosed, underscoring the need to improve early detection and diagnosis to ensure patients receive appropriate treatment sooner. The study also found that the majority of patients diagnosed were older adults, with a median age of 75 years, which highlights the importance of recognizing cardiac symptoms in elderly patients who may otherwise be misdiagnosed with more common cardiac conditions.     

Saurabh: Since more than half of the patients in both the US and Japan showed multiple cardiac symptoms, what does this mean for the clinical management and treatment of ATTR amyloidosis?   

Mina: More than half of patients in the US and Japan presented with multiple cardiac symptoms, such as heart failure, atrial fibrillation, and cardiomyopathy. This highlights the need for healthcare practitioners to recognize early symptoms and reduce diagnosis time, especially due to the systemic and progressive nature of ATTR. There is also a need to incorporate cardiac screening into the diagnostic process for patients with heart failure and other related symptoms, particularly when they do not respond to traditional therapies.     

Saurabh: The study found that the time to diagnosis was noticeably different between the US and Japan. What factors might be causing these regional differences?   

Mina: The OverTTuRe study revealed notable differences in the time to diagnosis, with delays of up to 2.5 years in the US and shorter delays in Japan (1.3 years) and the UK (1.7 years). Several factors may account for these regional differences, including variations in healthcare systems, public health policies, diagnostic approaches, and awareness of ATTR among healthcare professionals.    

Saurabh: How does AstraZeneca intend to use the findings from the OverTTuRe study to shape future clinical practices or guide further drug development for ATTR amyloidosis?   

Mina: The findings from the OverTTuRe study are an important addition to our understanding of the contemporary epidemiology of ATTR amyloidosis. We hope the insights gained from OverTTuRe will help the clinical community refine guidelines and practices by providing a more comprehensive view of how ATTR amyloidosis presents in diverse populations and highlighting the importance of cardiac manifestations.    

Our efforts in ATTR-CM are a key example of how we are aligning our heart failure (HF) strategy with our broader cardiovascular and renal disease ambitions. By understanding the root causes of heart failure and leveraging the data from studies like OverTTuRe, we are well-positioned to shape new approaches to transforming care and improving patient outcomes.    

Saurabh: How do the delays in diagnosis highlighted by the OverTTuRe study impact AstraZeneca's approach to positioning Wainua as an effective treatment for ATTR amyloidosis?   

Mina: The delays in diagnosis identified by the OverTTuRe study highlight the urgency of early detection and intervention in ATTR amyloidosis, particularly when cardiac symptoms are present. Due to the unmet need and high mortality of this disease, we are committed to developing the most comprehensive and rapidly expanding amyloidosis portfolio in the industry. We believe eplontersen has the potential to be a best-in-class treatment across ATTR amyloidosis phenotypes. It has already demonstrated sustained reductions in TTR protein levels, leading to its approval for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). We are now advancing our efforts with the CARDIO-TTRansform Phase III trial, which focuses on ATTR-CM.    

Saurabh: Considering the diverse cardiac symptoms highlighted in the study, how does Wainua address these different manifestations? Are there any plans to update treatment guidelines based on the study's insights into patient demographics and disease progression?  

Mina: We are running the largest ATTR-CM trial with more than 1,400 patients. The CARDIO-TTRansform Phase III trial is relevant for the cardiology community as ATTR-CM is a systemic, progressive, and fatal condition that can lead to progressive heart failure. We look forward to sharing further details when the data are anticipated to readout in 2026.   

About the Author: 

Mina Makar 

Mina Makar is the Senior Vice President and Commercial Lead of the Global Cardiovascular, Renal, and Metabolism (CVRM), BioPharmaceuticals Business Unit at AstraZeneca. In this role, Mina addresses the critical unmet needs in four interconnected disease areas: metabolism, heart failure, cardiovascular disease, and renal diseases. Through expanding the use of medicines today and developing the next wave of innovations while advancing the pipeline, he drives the ambition to improve and save lives for the millions of people who are living with the complexities of CVRM diseases. ​ 

His 30-year healthcare career began as a pharmacist and includes over two decades with AstraZeneca, encompassing experience in marketing and sales, payer and access strategies, as well as leadership and engagement. His previous role as SVP of US Respiratory & Immunology highlights a track record of achievement, including significant franchise growth and successful new product launches, such as the company's first respiratory biologic. ​ ​ 

Makar's dedication to the use of digital technologies and engaging with industry partners to transform science, has been pivotal to driving earlier diagnosis for CVRM patients, advancing understanding of disease drivers, and helping to bring medicines to patients faster. His leadership in CVRM extends to embedding sustainability into every initiative, from the laboratory to the patient to strengthen healthcare systems to be more accessible and resilient. 

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