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
Presenter |
Abstract title |
Presentation details |
|---|---|---|
Early CRVM research |
||
Venkateshvaran, A |
Impact of epicardial adipose tissue on cardiac hemodynamics and proteomics in heart failure with preserved ejection fraction: insights from the PROMIS-HFpEF study |
Chronic Heart Failure - Pathophysiology and Mechanisms 29 June 2021: 13.00 |
Lam, CSP |
Myeloperoxidase inhibitor AZD4831 target engagement and safety in a Phase IIa study in patients with heart failure with preserved ejection fraction (SATELLITE) |
Oral presentation Session: Chronic Heart Failure - Treatment 2 1 July 2021: 13.00 |
Michaëlsson, E |
Myeloperoxidase inhibition reverses the inflammatory proteomic pattern in heart failure with preserved ejection fraction |
Session: Chronic Heart Failure - Treatment 2 1 July 2021: 13.00 |
Grote Beverborg, N |
Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy |
Oral presentation Young Investigator Award: basic science |
Forxiga |
||
Docherty, KF |
Acute changes in estimated glomerular filtration rate following initiation of dapagliflozin in patients with heart failure and reduced ejection fraction: insights from DAPA-HF |
Oral presentation: Chronic Heart Failure - Pathophysiology and Mechanisms 2 30 June 2021: 13.00 |
McMurray, JJV |
Effect of Dapagliflozin vs Placebo on Symptoms and Six-Minute Walk Distance in Patients with Heart Failure: The DETERMINE Randomized Clinical Trials |
Oral presentation: Late-Breaking Trials 3 1 July 2021: 15.40 |
Savarese, G |
Eligibility for dapagliflozin and empagliflozin in real-world heart failure based on DAPA-HF, DELIVER, EMPEROR-Reduced and EMPEROR-Preserved selection criteria |
Oral presentation Registry Updates Session |
Qin, L |
Budget impact evaluation of the DAPA-HF trial: is dapagliflozin cost-saving for the treatment of heart failure with reduced ejection fraction? |
Oral presentation Abstract |
Docherty, KF |
Efficacy and safety of dapagliflozin in black, compared to white, patients with heart failure with reduced ejection fraction: Results from DAPA-HF |
Abstract |
Vanderheyden, M |
Real-world eligibility for dapagliflozin in unselected heart failure patients: Data from the CORDIS-HF registry |
Abstract |
RWE |
||
Savarese, G |
Heart Failure Drug Titration, Discontinuation and Mortality and HF Hospitalization Risk: A Multinational Observational Study (US, UK and Sweden) |
Oral presentation: Registry Updates |
Bodegård, J |
The risk of all-cause death after COVID-19 hospital admission among patients with prior heart failure, chronic kidney disease and cardiorenal syndrome: a 12 month follow-up observational study |
Oral presentation: Registry Updates |
Maggioni, AP |
Clinical course and related costs of patients with type 2 diabetes and heart failure and/or chronic kidney disease, drawn from a sample of more than 7 million people |
Registry Updates |
Taveira-Gomes, T |
Cardiorenal syndrome and death risk in patients with heart failure or chronic kidney disease: an unmet cardiorenal need? |
Abstract |
Gavina, C |
Prevalence and characterization of Heart Failure in a population of integrated care users |
Abstract |
Hunt, PR, Duong, M |
Healthcare related resource use and costs among patients with new diagnosis of Heart Failure in Germany: a retrospective cohort study using AOK PLUS data - part of the HF-BoI Project |
Abstract |
Hunt, PR, Duong, M |
Heart-Failure related hospitalisation and cardiovascular events among patients with incident heart failure in Germany: a retrospective cohort study using AOK PLUS data part of the HF-BoI Project |
Abstract |
Duong, M |
Describing patient characteristics and the incidence and prevalence of heart failure in Germany: a retrospective database study using AOK Plus - part of the HF-BoI Project |
Abstract |
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
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).
2. Mozaffarian D et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation 2016; 133(4):e38-360.
3. 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.
4. 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
5. Oktay AS and Shah SJ. Diagnosis and Management of Heart Failure with Preserved Ejection Fraction: 10 Key Lessons. Curr Cardiol Rev. 2015 Feb; 11(1): 42–52.
6. 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.
7. Azad N, Lemay G. Management of chronic heart failure in the older population. J Geriatr Cardiol 2014; 11(4):329–37.
Veeva ID: Z4-34937
Date of Preparation: June 2021