NewsMedical spoke with Mina Makar, Senior Vice President of Global CVRM at AstraZeneca, about groundbreaking research in Heart Failure and Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM). Mina shares insights on AstraZeneca’s mission to address unmet needs in cardiovascular care and the future of personalized medicine.
Firstly, please introduce yourself and tell us about your career to date
I hold the role of Senior Vice President, Global Cardiovascular, Renal and Metabolism (CVRM) in the BioPharmaceuticals Business Unit at AstraZeneca. In this role, I address the unmet needs in four inter-related disease areas: metabolism, heart failure, cardiovascular disease, and renal diseases, helping to drive our ambition to stop, reverse, and cure these chronic, progressive, and often devastating diseases by maximizing our medicines, delivering innovative solutions and advancing our pipeline.
I began my 30-year career in healthcare as a pharmacist and have since helped to bring important medicines to people who have very few or limited options. I’ve joined the CVRM team with deep experience in marketing and sales, payer and access strategies, and leadership and engagement. Recognizing the deep commitment we have in this important therapy area, I look forward to leading AstraZeneca into the future of CVRM care for the millions of people globally living with these conditions.
I’m so proud of the work we are doing to address existing unmet medical needs and set the future of CVRM care. Our collective success is what happens when our work reflects our passion.
Image Credit: sasirin pamai/Shutterstock.com
Click here to read more from AstraZeneca: Early Diagnosis and Intervention in Heart Failure with Prof. Martin Cowie & Dr. Lisa Anderson
To start, could you give us an overview of AstraZeneca's broader vision of addressing the unmet needs across cardiovascular, renal, and metabolism diseases, as well as how your team’s work aligns with this mission?
AstraZeneca is investing in the broadest and deepest portfolio and pipeline of CVRM medicines to slow and stop disease, protect vital organs and address major risk factors. We are uniquely positioned with a diverse portfolio based on novel and established biology, creating innovative combinations to address multiple risk factors/co-morbid disease in patients.
For example, by building on the success of Forxiga (dapagliflozin), the first SGLT2 inhibitor to demonstrate a mortality benefit in chronic kidney disease (CKD) and heart failure (HF) regardless of ejection fraction (EF), we are now utilizing next wave innovation to assess the use of the drug in novel dual mechanism combinations across five indications, tackling the complex challenges and unmet needs of comorbidities in cardiorenal patients. These programs aim to provide more options for patients who may not benefit from existing treatment guidelines for interconnected CVRM disease.
AstraZeneca has been presenting compelling data on amyloidosis. Next up is the CARDIO-TTRansform trial on transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). Could you explain the significance of this trial and its potential to reshape the treatment landscape for ATTR-CM?
The phase 3 CARDIO-TTRansform trial is the largest, most comprehensive trial in ATTR-CM to date. With over 1,400 patients enrolled, it is designed to deliver the most robust data in a broad patient population, including those on or naïve to stabilizers, representing the dynamic and evolving ATTR-CM treatment landscape.
The trial's results, expected in 2026, will provide further insights into the safety and efficacy of eplontersen for treating cardiomyopathy in patients living with hereditary or wild-type amyloidosis. We hope this will help progress the development of a novel RNA-targeted treatment designed to reduce the production of TTR protein at its source in the liver.
The CARDIO-TTRansform study includes a cardiac magnetic resonance (CMR) sub-analysis, which is considered the largest CMR study in ATTR-CM patients. How might these findings impact the way we evaluate and treat cardiac amyloid burden in the future?
The CARDIO-TTRansform phase 3 trial uses cardiac magnetic resonance (CMR) with extracellular volume (ECV) imaging to track treatment response in patients with cardiac amyloidosis (ATTR-CM) by assessing changes in cardiac amyloid burden along with associated changes in structure and function.
This non-invasive form of imaging navigates the limitations of other similar applications, provides accurate quantitative assessment readouts of key biomarkers, and is a viable option in renal failure, a complication often seen with amyloidosis.
The use of this method provides an important source of diagnosis, therapeutic and prognostic decision-making in the clinic when assessing cardiac amyloid burden. Therefore, findings from this sub-analysis will not only provide us with more information about the potential of eplontersen in ATTR-CM, but it will also help inform our future programs in other interconnected CVRM diseases, bolstering chances of improving patient outcomes in the area.
With real-world evidence from the OverTTuRe study indicating that the diverse presentation of ATTR-CM often leads to delayed diagnosis and treatment, what steps are AstraZeneca taking to improve early detection and patient outcomes?
At AstraZeneca, our ultimate pursuit is to pioneer new therapies in CVRM to slow and stop disease, protect vital organs, and address major risk factors. The latest findings from the OverTTuRe study reinforce the gaps that remain between early clinical manifestations and definitive diagnosis of ATTR-CM that could make a meaningful difference to patients.
To combat these challenges, we are transforming science and developing innovative screening and detection methods in partnership with healthcare practitioners, patient communities, governments, and policymakers to diagnose patients earlier. This is enabling us to advance our understanding of disease drivers through artificial intelligence and big data analytics while reshaping clinical trials to bring novel medicines to patients faster.
One of the presentations at the European Society of Cardiology (ESC) 2024 Congress highlighted a 2.9x increase in the diagnosis of cardiac amyloidosis in the UK between 2004 and 2021. What are the key factors driving this increased awareness, and how can healthcare systems further improve diagnosis rates globally?
We have already seen significant progress in heart failure research with translational advances resulting in increased therapeutic options for patients. As a result, we are now seeing the emergence of a range of engagement initiatives that are committed to cutting time to diagnosis and treatment intervention, particularly at the community level.
Through our unique engagement approach with key external partners like academic institutions, we are developing screening and detection methods to diagnose patients early and advance our understanding of disease drivers through AI and big data analytics. For example, Project OPERA investigates the use of AI-assisted echocardiography, while our SYMPHONY program is set to enroll patients in community-based studies to expand operational efficiencies with AI.
We are also working with the broader healthcare community to transform amyloidosis through our Accelerate Change Together (ACT) on Amyloidosis program. This program aims to halve the time to a heart failure diagnosis by 2028 and double the diagnosis rates of ATTR-CM by 2030.
Heart failure with preserved ejection fraction (HFpEF) has been a challenging condition to treat. With the growing understanding that ATTR-CM may be a significant underlying cause of HFpEF, how might AstraZeneca’s research influence the development of therapies for this subset of heart failure patients?
The heart failure landscape has undergone significant transformation in recent times. Scientific advances have led to greater understanding of the disease. We now know that heart failure has many different stages and types, and our knowledge of the disease's genetics and biology has grown. These advances have allowed us to gain further insight into what is driving the disease, providing the possibility of tailoring treatment regimens for subgroups of patients with a specific combination of disease drivers.
The latest findings from the OverTTuRe study suggest that many patients may have been presenting with early signs of ATTR-CM without being accurately diagnosed. This underscores the need to improve early detection and diagnosis to ensure patients receive appropriate treatment sooner.
AstraZeneca is well-known for its commitment to addressing multiple interrelated risk factors in cardiovascular, renal, and metabolism diseases. How does the integration of research across these disease areas drive innovative solutions that can improve patient outcomes holistically?
CVRM diseases affect 1.4 billion people globally, yet remain undiagnosed, undertreated, and their connections underrecognised. This makes the integration of research across these disease areas particularly important to help drive innovation and improve patient outcomes.
At AstraZeneca, we understand the importance of integrating research across all areas of CVRM. By using technologies such as AI and big data analytics, we are bolstering clinical trials to help bring novel therapies to patients who need them the most.
We are excited by our rich phase 2/3 pipeline, which employs next-wave innovation to address CVRM disease and associated comorbidities. Our emerging weight management portfolio is positioned to go beyond short-term weight loss with AZD5004, a potential first-in-class GLP-1 receptor agonist (GLP-1 RA), and AZD6234, our long-acting amylin analog (LAA). Likewise, our oral PCSK9 inhibitor, AZD0780, aims to drive reductions in LDL-C levels not achievable by statins alone.
As someone with extensive experience across multiple therapy areas, what do you find most exciting about the current trajectory of cardiovascular and heart failure research at AstraZeneca?
I am extremely excited by recent developments in our cardiovascular portfolio, and we are experiencing great momentum on the Wainua brand. The NEURO-TTRansform phase 3 trial has successfully served as the basis for approvals in the US and other markets for ATTRV-PN and is supporting Wainua’s current review for the indication in additional countries worldwide. Simultaneously, our CARDIO-TTRansform phase 3 trial is fully enrolled, making it the largest ATTR-CM trial.
We are also leveraging the strength of Forxiga, which we have advanced from a leading diabetes medicine to be the first to save lives in both heart failure and chronic kidney disease. Dapagliflozin acts as the foundational cardio-kidney metabolic treatment for our novel dual mechanism combinations across five indications, all progressing rapidly with phase 3 programs. It’s exciting to see the application of next-generation innovation helping to provide better outcomes for patients.
Looking ahead, how do you see AstraZeneca’s advancements in ATTR-CM and the broader CVRM field shaping the future of patient care, especially as the company continues to focus on innovative therapies and personalized medicine?
With double-digit growth year over year, we are confident in our existing medicines in the mid-term and the rich phase 2 and phase 3 pipeline in our hands today. We continue to strengthen our position in CVRM drug development predominantly through the success of Forxiga, which has established itself globally as the foundational treatment across three disease areas of chronic kidney disease, heart failure, and type 2 diabetes.
This is important to our future pipeline as we expect that 60 million patients who currently use Forxiga will be eligible for one of our dapagliflozin combination therapies at the time of launch.
We are taking a leading role in the CVRM field by highlighting the importance of rapid and accurate diagnosis and treatment intervention and expanding the range of innovative and personalized treatment options available to patients based on the success of our established portfolios. By putting these into practice, I believe we will go a long way to improving patient outcomes and reducing the increasing burden associated with this group of diseases.
Where can readers find more information?
Please see here for more information regarding AstraZeneca’s work in Heart Failure.
About 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. He has experience in marketing and sales, payer and access strategies, 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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