Forxiga approved in China to reduce the risk of cardiovascular death and hospitalisation in adult patients with symptomatic chronic heart failure

Forxiga approved in China to reduce the risk of cardiovascular death and hospitalisation in adult patients with symptomatic chronic heart failure

The first and only heart failure therapy with a proven mortality benefit now approved for patients with heart failure regardless of ejection fraction status
 

Forxiga (dapagliflozin) has been approved in China to reduce the risk of cardiovascular death, hospitalisation for heart failure (HF), or urgent HF visits in adults with symptomatic chronic HF. Forxiga has previously been approved in China for HF patients with reduced ejection fraction (HFrEF) meaning that Forxiga is now approved in China to reduce the risk of cardiovascular death and hospitalisations in adult patients with symptomatic chronic HF regardless of ejection fraction phenotype.

The approval by China’s National Medical Products Administration (NMPA) is based on positive results from the DELIVER Phase III trial. Results from the prespecified pooled analysis of DELIVER and DAPA-HF Phase III trials also established dapagliflozin as the first HF medication to demonstrate a mortality benefit across the full ejection fraction range.1,2

Ruud Dobber, Executive Vice President, and President BioPharmaceuticals Business Unit, AstraZeneca, said: “This broader indication for Forxiga in adults with symptomatic chronic heart failure across the full ejection fraction range is a significant advancement for patients. It represents an exciting turning point in the battle against heart failure given the unmet treatment needs and the absence until now of treatments that reduce mortality in this setting. Importantly, this development underscores our commitment to accelerating earlier detection and coordinated care, to address the complexities of heart failure across the disease spectrum.”

HF is a complex syndrome that occurs when the heart cannot pump enough blood around the body.3 HF affects approximately 4.5 million people in China.4 Around half of HF patients die within five years of diagnosis.5 Patients with ejection fraction above 40% are at greater risk of death and hospitalisation and experience an especially high burden of symptoms and physical limitations, and consequently have a poor quality of life.6 The economic burden of HF in China is huge in terms of healthcare costs and resource utilisation, and hospitalisation is the major contributor to the HF treatment burden - the mean hospital stay for HF patients is 30 days in one year.7

Forxiga is also approved for the treatment of patients with T2D, HFrEF and CKD in more than 100 countries around the world including China, Japan, the US, and the EU.

Notes

Heart Failure
Heart Failure (HF) is a chronic, long-term condition that worsens over time.8 It affects nearly 64 million people globally9 and is associated with substantial morbidity and mortality.10 Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.11 There are several types of HF often defined by left ventricular ejection fraction (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%).12 Approximately half of all HF patients have HFmrEF or HFpEF, with few therapeutic options available.13

DELIVER 
DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure) 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 above 40%, with or without type 2 diabetes (T2D). DELIVER is the largest clinical trial to date in HF patients with LVEF above 40%, with 6,263 randomised patients.14 Results from the DELIVER Phase III trial showed that Forxiga met its primary endpoint in reducing the composite outcome of cardiovascular (CV) death or worsening HF by 18% (16.4% in the Forxiga group and 19.5% in the placebo group over a median follow-up of 2.3 years [hazard ratio {HR} =0.82 {95% CI 0.73-0.92}; p<0.001, ARR 3.1%]).14

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 T2D, designed to evaluate the effect of Forxiga 10mg, compared with placebo, given once daily in addition to standard of care. 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.15 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).15

Forxiga (dapagliflozin)
Forxiga is a first-in-class, oral, once-daily selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2). Forxiga is indicated to reduce the risk of cardiovascular death, hospitalisation for HF, or urgent HF visits in adults with symptomatic chronic heart failure.16 Forxiga is also approved in China for adults with chronic kidney disease (CKD) and for the treatment of insufficiently controlled type 2 diabetes (T2D) as an adjunct to diet and exercise.  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 pancreas.15, 17-18 Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF, and CKD.3, 9, 19-20

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, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.

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 social media @AstraZeneca

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References

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10. Mozaffarian D, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):e38-360.

11. McDonagh T, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;00:1-128.

12. 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.  Journal of American College of Cardiology. 2008;10(10):933-989.

13. Kosiborod MN, et al. The effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and mildly reduced or preserved ejection fraction: results from the DELIVER Trial. Presented at: American Heart Association (AHA) Scientific Sessions 2022, 5-7 November 2022, Chicago, Illinois, USA.

14. 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.

15. McMurray JJV, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.

16. Forxiga Prescribing Information.

17. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446. 

18. 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.

19. Centers for Disease Control and Prevention (CDC) [Internet]. A snapshot: Diabetes in the United States; [cited 2023 Aug 1]. Available from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.

20. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet]. Heart disease & kidney disease; [cited 2023 Aug 1]. Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease.