Farxiga featured in 12 simultaneous publications in conjunction with the European Society of Cardiology scientific sessions
Data show Farxiga is the first heart failure treatment demonstrating consistent cardiovascular mortality benefit across the full ejection fraction range
EVOLUTION HF includes data on more than 250 000 patients and is the first study on adoption of guideline-directed medical therapies in clinical practice
Today the final publication relating to AstraZeneca’s scientific sessions at the recent European Society of Cardiology (ESC) annual meeting was issued, bringing the total number of publications in peer-reviewed journals to 121-12. Eleven of these publications relate to the landmark Phase III trial DELIVER, which showed that Farxiga (dapagliflozin) on top of standard of care reduced the composite of cardiovascular (CV) death or worsening heart failure (HF) in patients with HF and mildly reduced or preserved ejection fraction (EF), by 18% compared to placebo (p<0.001, 16.4% in the dapagliflozin group and 19.5% (absolute risk reduction [ARR] 3.1%) in the placebo group over a median follow-up of 2.3 years)1.
In addition to the primary publication on DELIVER in New England Journal of Medicine, a pre-specified pooled analysis, including also DAPA-HF, published in Nature Medicine showed that Farxiga, on top of standard of care, demonstrated reduction in CV death by 14% (p=0.01, ARR 1.5%) and reduction in death from any cause by 10% (p=0.03, ARR 1.5%) versus placebo in patients with HF irrespective of EF, making Farxiga the first HF medication to ever demonstrate a CV mortality benefit across the entire EF range2. The safety and tolerability of Farxiga was consistent with the well-established safety profile of the medicine.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said:
“Heart failure is one of the leading causes of hospitalisations and death worldwide, affecting 64 million people. These new results validate the clinical value and differentiation of Farxiga in heart failure patients as a treatment which can be initiated immediately while waiting for ejection fraction to be measured. This marks an unprecedented number of simultaneous data publications in prestigous journals and underscores the importance of the DELIVER and DAPA-HF trial data.”
The 12th and final publication stemming from AstraZeneca’s scientific presentations at ESC was issued today in Journal of the American Colleague of Cardiology: Heart Failure, demonstrating an urgent need for earlier use of novel guideline-directed medical therapies, which currently in clinical practice are utilised too late, too little and too slow, even though treatments like Farxiga offers important benefits to improve patients’ lives. The full list of publications comprise as follows:
Notes
HF
HF is a chronic, long-term condition that worsens over time15. It affects nearly 64 million people globally and is associated with substantial morbidity and mortality16,17. Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden18. 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: HF with reduced EF (HFrEF, LVEF less than or equal to 40%), HF with mildly reduced EF (HFmrEF, LVEF 41-49%) and HF with preserved EF (HFpEF, LVEF greater than or equal to 50%)19. Approximately half of all HF patients have HFmrEF or HFpEF, with few therapeutic options available19,20.
EVOLUTION HF
EVOLUTION HF is the first study to describe dapagliflozin and other GDMTs in the treatment of heart failure after market approvals in three different countries across the globe (Japan, Sweden and US). It is a real-world study of >250,000 contemporary patients newly initiated with a GDMT during years 2020-2022 following a hospitalisation for heart failure (hHF) discharge.
DAPA-HF
DAPA-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 type-2 diabetes (T2D), designed to evaluate the effect of Farxiga 10mg, compared with placebo, given once daily in addition to standard of care (SoC) consisting of an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). 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 CV death. The median duration of follow-up was 18.2 months21.
The secondary endpoint included the total number of 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)21.
DELIVER
DELIVER was an international, randomised, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of Farxiga, compared with placebo, in the treatment of HF patients with LVEF greater than 40%, with or without T2D. Farxiga 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 a sodium-glucose cotransporter 2 (SGLT2) inhibitor)22. DELIVER is the largest clinical trial to date in HF patients with LVEF above 40%, with 6,263 randomised patients22.
The primary endpoint was the time to first occurrence of CV death, hHF or an urgent HF visit. The secondary endpoint includes 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 cause22.
Farxiga
Farxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor. Research has shown Farxiga’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas21,23,24. Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and chronic kidney disease (CKD)16,25-27.
Farxiga is approved in adults and children aged 10 years and above for the treatment of insufficiently controlled type-2 diabetes mellitus as an adjunct to diet and exercise. Farxiga is also approved for the treatment of HFrEF and the treatment of CKD based on the findings of the DAPA-HF and DAPA-CKD Phase III trials.
DapaCare is a robust programme of clinical trials to evaluate the potential CV, renal and organ protection benefits of Farxiga. It includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience. Farxiga is currently being tested in patients without T2D following an acute myocardial infarction or heart attack in the DAPA-MI Phase III trial - a first of its kind, indication-seeking registry-based randomised controlled trial.
AstraZeneca in CVRM
Cardiovascular, 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.
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, 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.
Contacts
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.
References
1. Solomon S, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med 2022.
2. Jhund P, et al. Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level meta-analysis of DAPA-HF and DELIVER. Nature Medicine.
3. Vaduganathan M, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet 2022.
4. Cunningham J, et al. Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction. J Am Coll Cardiol 2022.
5. Butt J, et al. Dapagliflozin, atrial fibrillation, and heart failure with mildly reduced or preserved ejection fraction in DELIVER. J Am Coll Cardiol 2022.
6. Vaduganathan M, et al. Estimated Event-Free Survival Benefits with Dapagliflozin in HF with Mildly Reduced or Preserved Ejection Fraction. J Am Coll Cardiol 2022.
7. Butt J, et al. Efficacy and Safety of Dapagliflozin According to Frailty in Patients with Heart Failure: A Prespecified Analysis of the DELIVER Trial. Circulation 2022.
8. Adamson C, et al. Dapagliflozin for heart failure according to body mass index: the DELIVER trial, European Heart Journal 2022.
9. Myhre P, et al. Influence of NT-proBNP on Efficacy of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. J Am Coll Cardiol HF.
10. Ostrominski JW, et al Dapagliflozin and New York Heart Association functional class in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial. European Journal of Heart Failure 2022.
11. Peikert A, et al. Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial. Circ Heart Fail 2022.
12. Margulies KB, et al. DELIVERing Progress in Heart Failure with Preserved Ejection Fraction. NEJM 2022.
13. Lam C, et al. DELIVERing Therapeutic Efficacy Across the Ejection Fraction Spectrum of Heart Failure. Circulation 2022.
14. Savarese G, et al. Heart Failure Drug Treatment – Inertia, Titration and Discontinuation: A Multinational Observational Study. J Am Coll Cardiol HF.
15. Cleveland Clinic [Internet]. Heart failure; [cited 2022 Jul 14] Available from:
https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure
16. 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):1211–59.
17. Mozaffarian D, et al. Heart disease and stroke statistics—2016 update. Circulation. 2016; 133(4):e38–360.
18. Azad N, et al. Management of chronic heart failure in the older population. J Geriatr Cardiol. 2014; 11(4):329–37.
19. 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. 2022;79(17):e263-421.
20. Dunlay SM, et al. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol 2017;14(10):591–602.
21. McMurray JJV, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381(21):1995–2008.
22. 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):1217–25.
23. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020; 383(15):1436–46.
24. 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):347–57.
25. Mayo Clinic [Internet]. Heart failure, 2020; [cited 2022 Jul 14]. Available from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
26. Centers for Disease Control and Prevention (CDC) [Internet]. A snapshot: Diabetes in the United States, 2020; [cited 2022 Jul 14]. Available from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.
27. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet]. Heart disease & kidney disease, 2016; [cited 2022 Jul 14]. Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease
Veeva ID: Z4-48373
Date of preparation: September 2022