A new subgroup analysis from the ground-breaking DAPA-CKD Phase III trial showed that AstraZeneca's Farxiga (dapagliflozin), on top of standard of care, reduced the composite of worsening of kidney function or risk of cardiovascular (CV) or renal death in patients with chronic kidney disease (CKD), irrespective of the underlying cause of the disease.[1]

CKD is a serious, progressive condition defined by decreased kidney function.[2] It is estimated to affect nearly 700 million people worldwide, many of them still undiagnosed.[3-5] One in three adults in the US, or approximately 80 million people, are at risk of developing CKD.[5] The main causes of CKD are diabetes (38%), high blood pressure (26%) and glomerulonephritis (kidney inflammation, 16%).[6]

In the subgroup analysis, compared to placebo Farxiga showed a relative risk reduction (RRR) of 37% for patients whose CKD was primarily driven by diabetic kidney disease (absolute risk reduction [ARR] = 5.8%); 25% for high blood pressure (ARR = 2.2%); 57% for glomerulonephritis (ARR = 7.5%); and 42% for CKD of other or unknown causes (ARR = 5.0%) (p−interaction for RRR 0.53).[1] Similarly, Farxiga showed a reduction in all-cause mortality, a secondary outcome, compared to placebo regardless of underlying CKD cause (p-interaction 0.55).[1]

The safety and tolerability of Farxiga was consistent with the well-established safety profile of the medicine.

Prof. Hiddo L. Heerspink, co-chair of the DAPA-CKD trial and its Executive Committee, University Medical Center Groningen, the Netherlands, said: "These results reinforce the potential of Farxiga to change the standard of care for a wide range of patients with chronic kidney disease, regardless of the root cause of the disease. This could open up enormous possibilities for the millions of patients living with chronic kidney disease worldwide."

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "The DAPA-CKD trial showed the potential of Farxiga as the first SGLT2 inhibitor to significantly prolong survival in a renal outcomes trial in patients with chronic kidney disease with and without type-2 diabetes. The new data presented further demonstrate Farxiga's consistent and clinically meaningful benefit across a diverse group of patients with chronic kidney disease, a population in urgent need of new treatment options to slow the progression of their disease."

The data were presented at the American Society of Nephrology (ASN) Kidney Week Reimagined 2020.

Earlier this month (https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/farxiga-granted-breakthrough-therapy-designation-in-us-for-chronic-kidney-disease.html), Farxiga was granted Breakthrough Therapy Designation in the US for patients with CKD, with and without type-2 diabetes (T2D) and was recommended for approval (https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/forxiga-recommended-for-approval-in-the-eu-by-chmp-for-heart-failure.html) in the EU by the Committee for Medicinal Products for Human Use for heart failure (HF). Additionally, in May 2020 (https://www.astrazeneca.com/media-centre/press-releases/2020/farxiga-approved-in-the-us-for-the-treatment-of-heart-failure-in-patients-with-heart-failure-with-reduced-ejection-fraction.html), Farxiga was approved in the US to reduce the risk of CV death and hospitalisation for heart failure (hHF) in adults with HF (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D.

Chronic kidney disease 

CKD is a serious, progressive condition defined by decreased kidney function (shown by reduced estimated glomerular filtration rate [eGFR] or markers of kidney damage, or both, for at least three months).[2] In its most severe form, known as end-stage kidney disease (ESKD), kidney damage and deterioration of kidney function have progressed to the stage where dialysis or kidney transplantation are required.[7] The majority of patients with CKD will die from CV causes before reaching ESKD.[8][ ]

DAPA-CKD

DAPA-CKD is an international, multi-centre, randomised, double-blinded trial in 4,304 patients designed to evaluate the efficacy of Farxiga 10mg, compared with placebo, in patients with CKD Stages 2-4 and elevated urinary albumin excretion, with and without T2D. Farxiga was given once daily in addition to standard of care. Detailed results shared (https://www.astrazeneca.com/media-centre/press-releases/2020/farxiga-demonstrated-reduction-in-the-risk-of-kidney-failure-and-cardiovascular-or-renal-death-in-patients-with-ckd-in-the-phase-iii-dapa-ckd-trial.html) in August 2020 and published (https://www.nejm.org/doi/full/10.1056/NEJMoa2024816?query=main_nav_lg) in The New England Journal of Medicine showed Farxiga reduced the primary composite endpoint of worsening of renal function (defined as a composite of a sustained ≥50% eGFR decline, onset of ESKD and death from CV or renal cause) or renal or CV death by 39% compared to placebo (p<0.0001). The results were consistent in patients both with and without T2D. Farxiga also met all secondary endpoints including the time to first occurrence of the renal composite (sustained ≥50% eGFR decline, ESKD and renal death), the composite of CV death or hHF, and death from any cause by 31% (ARR = 2.1%, p=0.0035).[9]

Farxiga 

Farxiga (dapagliflozin) is a first-in-class, oral, once-daily sodium-glucose co-transporter-2 (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-TIMI 58 CV outcomes trial in adults with T2D, Farxiga reduced the risk of the composite endpoint of hHF or CV death versus placebo, when added to standard of care.

Farxiga is currently being assessed in patients with HF in the DELIVER (HF with preserved ejection fraction, HFpEF) and DETERMINE (HFrEF and HFpEF) trials, as well as in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI trial - a first of its kind, indication-seeking registry-based randomised controlled 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 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, primarily for the treatment of diseases in three therapy areas - Oncology, 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 (http://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca).

Contacts

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References

1. Wheeler DC. Effects of dapagliflozin on kidney function, cardiovascular events and all-cause mortality according to cause of kidney disease in the DAPA-CKD trial. Oral abstract #FR-OR58 presented at: American Society of Nephrology - Kidney Week 2020 Reimagined, 19-25 October 2020.
2. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney International Supplement 2012; 2:279-335.
3. Bikbov B et al. Global, regional, and national burden of chronic kidney disease, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet 2020; 395(10225):709-33.
4. Hirst JA et al. Prevalence of chronic kidney disease in the community using data from OxRen: A UK population-based cohort study. Br J Gen Pract 2020; 70(693):e285-e293.
5. National Kidney Foundation. Kidney Disease: The Basics; 2020 [cited 22 October 2020]. Available from: URL: https://www.kidney.org/news/newsroom/factsheets/KidneyDiseaseBasics.
6. National Institute of Diabetes and Digestive and Kidney Diseases. High Blood Pressure & Kidney Disease: National Institutes of Health [cited 22 October 2020]. Available from: URL: https://www.niddk.nih.gov/health-information/kidney-disease/high-blood-pressure.
7. Centers for Disease Control and Prevention (CDC). Chronic Kidney Disease in the United States, 2019; 11 March 2019 [cited 22 October 2020]. Available from: URL: https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.html.
8. Briasoulis A, Bakris GL. Chronic Kidney Disease as a Coronary Artery Disease Risk Equivalent. Current Cardiology Reports 2013; 15(3):340.
9. Heerspink HJL et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020; 383(15):1436-46.