New data at Heart Failure 2021 showcases AstraZeneca’s leading and diverse heart failure portfolio

Company continues to deliver on its commitment to address unmet clinical needs in heart failure

AstraZeneca is sharing encouraging clinical trial results on AZD4831, its investigational, first-in-class myeloperoxidase (MPO) inhibitor for heart failure with preserved ejection fraction (HFpEF), along with other early stage research, at Heart Failure 2021 online congress, 29 June to 1 July 2021. Also presented will be new pre-clinical data on phospholamban (PLN)-antisense oligonucleotide (ASO), as a novel therapeutic approach that offers a precision medicine strategy in heart failure (HF).

Regina Fritsche Danielson, Senior Vice President and Head of Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, said: “We are excited by the promising results we are seeing in our long-term heart failure research programmes. At AstraZeneca we have a leading pipeline that leverages cutting-edge platforms from antisense oligonucleotides to cell therapy and first-in-class small molecules, such as AZD4831, and we look forward to bringing the next wave of medicines that aim to halt or reverse the damage of heart failure.”

HFpEF represents about half of all HF cases,¹ yet treatments remain very limited. HFpEF occurs when the heart is unable to fill with blood sufficiently, due to increased stiffness of the muscle in the left ventricle and its inability to relax. Although this stiffness is understood to be triggered by a number of factors, HFpEF is associated with inflammation affecting the body and heart. Research has shown that MPO-derived oxidants contribute to tissue damage, inflammation and fibrosis. At Heart Failure 2021, encouraging data from AZD4831’s Phase IIa SATELLITE trial on target engagement will be presented.

In addition, pre-clinical efficacy data will be presented on PLN-ASO which targets the drivers of disease involved in calcium cycling, a key pathway for heart muscle contraction and relaxation. Although PLN/SERCA2a are well-accepted as HF targets, to date no pharmacological strategy based on these targets has been successful. Our goal is to leverage the full potential of ASOs as novel therapeutic interventions, supported by our deep understanding of the biology of disease.

At Heart Failure 2021, 18 abstracts, including nine oral presentations, will be shared.

AstraZeneca presentations at Heart Failure 2021

Heart failure

HF is a chronic disease where half of patients will die within five years of diagnosis.² HFpEF occurs when the heart is unable to fill with blood sufficiently, due to increased stiffness of the muscle in the left ventricle and its inability to relax. HFpEF represents about half of all HF cases,^3,4 and is highly prevalent in patients with hypertension, diabetes, obesity, metabolic syndrome or chronic kidney disease.⁵ HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer).⁶ Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.⁷

 AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three therapy areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and metabolism, AstraZeneca is investing in a portfolio of medicines for organ protection and improved outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines in Oncology and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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References

1   Dunlay, S., Roger, V. & Redfield, M. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol 14, 591–602 (2017).

1. Mozaffarian D et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American  Heart Association. Circulation 2016; 133(4):e38-360.
2. Lam C, Chandramouli C, Ahooja V, Verma S. SGLT-2 Inhibitors in Heart Failure: Current Management, Unmet Needs, and Therapeutic Prospects. Journal of American Heart Association. 2019; 8(20):e013389.
3. Lam C, Voors AA, de Boer RA, Solomon SD, van Veldhuisen DJ. Heart failure with preserved ejection fraction: from mechanisms to therapies. European Heart Journal. 2018;39(30):2780-92
4. Oktay ASand Shah SJ. Diagnosis and Management of Heart Failure with Preserved Ejection Fraction: 10 Key Lessons. Curr Cardiol Rev. 2015 Feb; 11(1): 42–52.
5. Mamas MA et al. Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. Eur J Heart Fail 2017; 19(9):1095–104.
6. Azad N, Lemay G. Management of chronic heart failure in the older population. J Geriatr Cardiol 2014; 11(4):329–37.

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