news/AZN/2023.02.08/Forxiga approved in the EU for the treatment of symptomatic chronic heart failure.txt

* First and only heart failure therapy with proven mortality benefit across the full ejection fraction rangeForxiga (dapagliflozin) has been approved in the European Union to extend the indication for heart failure (HF) with reduced ejection fraction (HFrEF) to cover patients across the full spectrum of left ventricular ejection fraction (LVEF), including HF with mildly reduced and preserved ejection fraction (HFmrEF, HFpEF).The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use in December 2022 and was based on the positive results from the DELIVER Phase III trial1. Results from the prespecified pooled analysis of DELIVER and DAPA-HF Phase III trials also established Forxiga as the first HF medication to demonstrate mortality benefit across the full ejection fraction range2.Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "This broader indication for Forxiga for the treatment of symptomatic chronic heart failure across the full ejection fraction range will help more patients to benefit from this well-tolerated and guideline-directed treatment. We are redefining treatment of cardiorenal diseases with Forxiga's demonstration of life-saving benefits, underscoring AstraZeneca's commitment to provide innovative solutions that can help address the complexities of heart failure across the spectrum of the disease."HF is a chronic, long-term condition that worsens over time3 and affects about 15 million people in Europe4. Approximately half of HF patients die within five years of diagnosis5 and patients with HFmrEF and HFpEF are not only at greater risk of death and hospitalisations but experience an especially high burden of symptoms and physical limitations, and a poor quality of life6.HFmrEF and HFpEF are also severely underdiagnosed as signs and symptoms are often nonspecific and overlapping with other clinical conditions7. These conditions are frequently complicated by multiple interrelated diseases, specifically coronary heart disease, obesity, diabetes, long-standing hypertension, and chronic kidney disease (CKD), highlighting the importance of risk management for patients with this complex syndrome7.Forxiga (known as Farxiga in the US) is approved for the treatment of patients with type-2 diabetes (T2D), HFrEF and CKD in more than 100 countries around the world including the US, the EU, China and Japan.It has most recently received regulatory approvals in Great Britain, Japan and Turkey to extend the HF indication to include patients across the full spectrum of LVEF. The HF indication extension application is currently under review in the US and other countries.NotesHFHF is a chronic, long-term condition that worsens over time3. It affects nearly 64 million people globally8 and is associated with substantial morbidity and mortality5. Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden9. There are several types of HF often defined by LVEF, a measurement of the percentage of blood leaving the heart each time it contracts, including: HFrEF (LVEF less than or equal to 40%), HFmrEF (LVEF 41-49%) and HFpEF (LVEF greater than or equal to 50%)7. Approximately half of all HF patients have HFmrEF or HFpEF, with few therapeutic options available7,10.DAPA-HFDAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) was an international, multi-centre, parallel-group, randomised, double-blinded Phase III trial in 4,744 patients with HFrEF, with and without T2D), designed to evaluate the effect of Forxiga 10mg, compared with placebo, given once daily in addition to standard of care (SoC). The primary composite endpoint was time to the first occurrence of a worsening HF event (hospitalisation or equivalent event, i.e. an urgent HF visit), or cardiovascular (CV) death. The median duration of follow-up was 18.2 months. Key secondary endpoints included the total number of hospitalisations for HF (hHF) (including repeat admissions) and CV deaths, change from baseline to 8 months in the total symptom score on the Kansas City Cardiomyopathy Questionnaire (KCCQ)11.DELIVERDELIVER was an international, randomised, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of Forxiga, compared with placebo, in the treatment of HF patients with LVEF greater than 40%, with or without T2D. Forxiga was given once daily in addition to background therapy (regional SoC for all comorbidities, including diabetes and hypertension, with the exception of concomitant use of SGLT2 inhibitor)12. DELIVER is the largest clinical trial to date in HF patients with LVEF above 40%, with 6,263 randomised patients12.The primary composite endpoint was the time to first occurrence of CV death, hHF or an urgent HF visit. Key secondary endpoints include the total number of HF events (hHF or urgent HF visit) and CV death, change from baseline in the total symptom score of the KCCQ at eight months, time to the occurrence of CV death and time to the occurrence of death from any cause12.ForxigaForxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor. Research has shown Forxiga's efficacy in preventing and delaying cardiorenal disease, while also protecting the organs - important findings given the underlying links between the heart, kidneys and pancreas11,13,14. Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and CKD8,15-17.Forxiga is approved in adults and children aged 10 years and above for the treatment of insufficiently controlled T2D mellitus as an adjunct to diet and exercise. Forxiga is also approved for the treatment of HFrEF in adults and the treatment of CKD in adults based on the findings of the DAPA-HF and DAPA-CKD Phase III trials.AstraZeneca in CVRMCardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca's main disease 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 pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving 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 CV health for millions of patients worldwide.AstraZenecaAstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, 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.ContactsFor details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.References1. Solomon S, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022; 387(12):1089-1098.2. Jhund P, et al. Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER. Nat Med. 2022; 28(9):1956-1964.3. Cleveland Clinic [Internet]. Heart failure [cited 2023 Jan 11]. Available from: https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure.4. Dickstein K, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008;10(10):933-989.5. Mozaffarian D, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):e38-360.6. Warraich HJ, et al. Physical function, frailty, cognition, depression, and quality of life in hospitalized adults >=60 years with acute decompensated heart failure with preserved versus reduced ejection fraction. Circ Heart Fail. 2018;11(11):e005254.7. Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2008;10(10):933-989.8. Vos T, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211-1259.9. Azad N, et al. Management of chronic heart failure in the older population. J Geriatr Cardiol. 2014;11(4):329-337.10. Dunlay SM, et al. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14(10):591-602.11. McMurray JJV, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.12. Solomon SD, et al. Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial. Eur J Heart Fail. 2021;23(7):1217-1225.13. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.14. Wiviott SD, et al; for the DECLARE-TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [article and supplementary appendix]. N Engl J Med. 2019;380(4):347-357.15. Mayo Clinic [Internet]. Heart failure [cited 2023 Jan 11]. Available from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.16. Centers for Disease Control and Prevention (CDC) [Internet]. A snapshot: Diabetes in the United States [cited 2023 Jan 11]. Available from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.17. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet]. Heart disease & kidney disease [cited 2023 Jan 11]. Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease..(C) 2023 M2 COMMUNICATIONS, source M2 PressWIRE