LATEST ACC DATA: Phase III Forxiga DAPA-HF Trial Sub-analysis shows consistent effect regardless of background therapy
Farxiga reduced the incidence of heart failure worsening or cardiovascular death in a sub-analysis from landmark Phase III DAPA-HF trial
New data showed consistent effect of Farxiga in patients with heart failure with reduced ejection fraction, regardless of background therapy
New data from a sub-analysis of the landmark Phase III DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial showed that AstraZeneca’s Farxiga (dapagliflozin) reduced the incidence of the primary composite endpoint of heart failure (HF) worsening or cardiovascular (CV) death compared to placebo, in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of their background therapy (i.e. other medications for heart failure).1
Farxiga was evaluated in patients who were receiving a broad range of pharmacological treatments, device therapies and cardiac resynchronisation therapy for HFrEF. A consistent reduction in the primary outcome was observed across all these treatment subgroups.1
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “These new data from the DAPA-HF trial further reinforce Farxiga’s clinical effects beyond diabetes. By reducing the risk of heart failure worsening regardless of background therapy, Farxiga has the potential to improve current standard of care and reduce the burden of disease for heart failure patients across the globe.”
The results were made available at the American College of Cardiology’s 69th Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC) and were published in the European Heart Journal.
Farxiga is indicated as a monotherapy and as part of combination therapies to improve glycaemic control in adults with T2D. In the US it is also approved to reduce the risk of hospitalisation for HF in patients with T2D and established CV disease or multiple CV risk factors.
In January 2020, the US Food and Drug Administration (FDA) accepted a supplemental New Drug Application (sNDA) and granted Priority Review for Farxiga to reduce the risk of CV death or the worsening of HF in adults with HFrEF with and without T2D. The Prescription Drug User Fee Act date, the FDA action date for this supplemental application, is scheduled for the second quarter of 2020.
HF is a life-threatening disease in which the heart cannot pump enough blood around the body.2 It affects approximately 64 million people worldwide, at least half of whom have a reduced ejection fraction, and is a chronic and degenerative disease where half of patients will die within five years of diagnosis.3,4 HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancers).5 It is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.6
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) is an international, multi-centre, parallel-group, randomised, double-blinded trial in patients with heart failure and reduced ejection fraction (LVEF ≤ 40%), with and without T2D, designed to evaluate the effect of Farxiga 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 heart failure event (hospitalisation or equivalent event; i.e. an urgent heart failure visit), or cardiovascular death.
Farxiga is a first-in-class, oral once-daily SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monotherapy and as part of combination therapy as an adjunct to diet and exercise to improve glycaemic control, with the additional benefits of weight loss and blood-pressure reduction. In the DECLARE CV outcomes trial in adults with T2D, Farxiga reduced the risk of the composite endpoint of hospitalisation for HF or CV death versus placebo, when both were added to standard of care.
In the DAPA-HF trial, Farxiga on top of standard of care reduced both the incidence of cardiovascular death and the worsening of heart failure in patients with HFrEF, with and without type-2 diabetes. Farxiga is also being investigated for patients with HF in the DELIVER (HFpEF) and DETERMINE (HFrEF and HFpEF) trials, as well as patients with CKD in the DAPA-CKD trial. Farxiga has a robust programme of clinical trials that 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.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM) together 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 pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling comorbidities. 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.
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- Docherty KF et al. 2020 Consistent Benefit of Dapagliflozin According to Background Therapy in Patients with HFrEF: An Analysis of the DAPA-HF Trial. Presented at the American College of Cardiology’s 69th Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC); 28 March – 30 March, Chicago.
- Mayo Clinic. Heart failure; 2017 [cited 2020 Mar 24]. Available from URL: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
- Travessa AMR, Menezes Falcão LF de. Treatment of Heart Failure With Reduced Ejection Fraction-Recent Developments. Am J Ther 2016; 23(2):e531-49.
- Mozaffarian D et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation 2016; 133(4):e38-360.
- Mamas, M. A., Sperrin, M., Watson, M. C., Coutts, A., Wilde, K., Burton, C., ... Myint, P. K. (2017). Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. European Journal of Heart Failure, 19(9), 1095-1104. https://doi.org/10.1002/ejhf.822
- Azad N, Lemay G. Management of chronic heart failure in the older population. J Geriatr Cardiol 2014; 11(4):329–37.