Farxiga study showed reduced progression of kidney disease or renal death in patients with type-2 diabetes

10 June 2019
 

Farxiga showed a 47% reduction in the composite of kidney function decline, end-stage renal disease or renal death in a pre-specified analysis from DECLARE-TIMI 58

A pre-specified exploratory analysis of renal data from the Phase III DECLARE-TIMI 58 trial, the broadest cardiovascular outcomes trial of a sodium-glucose co-transporter 2 (SGLT2) inhibitor, showed that Farxiga (dapagliflozin) reduced the progression of kidney disease or renal death in patients with type-2 diabetes (T2D).

These data, presented today at the American Diabetes Association (ADA) 79th Scientific Sessions, San Francisco, USA, and simultaneously published in The Lancet Diabetes & Endocrinology, showed a 47% reduction with Farxiga in the relative risk of the composite renal-specific outcome of kidney function decline (sustained ≥40% decrease in estimated glomerular filtration rate [eGFR] to <60 mL/min/1.73m²), end-stage renal disease (ESRD), or renal death (excluding cardiovascular death) compared to placebo (1.5% vs. 2.8%; HR 0.53 [95% CI 0.43-0.66]).¹

Additionally, Farxiga reduced the relative risk of a cardio-renal composite of kidney function decline, ESRD, or renal or cardiovascular (CV) death by 24% compared to placebo (4.3% vs. 5.6%; HR 0.76 [95% CI 0.67-0.87]).¹

This analysis evaluated 17,160 patients with T2D and predominantly preserved renal function, irrespective of underlying atherosclerotic CV disease (ASCVD). People with diabetes have a six-to-twelve times higher risk of developing ESRD and are approximately twice as likely to develop chronic kidney disease (CKD) than those without.^2,3

Elisabeth Björk, Senior Vice President, Head of Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said: “Heart failure and renal diseases are two of the most common and early complications experienced by people living with type-2 diabetes, and are too often overlooked. They contribute to a growing economic burden on the global healthcare system and can lead to fatal outcomes for patients. These data continue to offer clinically relevant evidence of the early cardio-renal effects of Farxiga.”

While ESRD was a rare event in the trial, the incidence was lower in the Farxiga arm compared to placebo (0.1% vs. 0.2%; HR 0.31 [95% CI 0.13-0.79]). The renal-specific outcome was consistent across subgroups regardless of eGFR or urinary albumin-to-creatinine ratio (UACR) category, whether they had established ASCVD or multiple CV risk factors.¹

These data were presented alongside other clinically important renal outcomes data from the DECLARE-TIMI 58 trial, including positive results from another sub-analysis that evaluated UACR, a key marker of kidney health. Farxiga improved renal function as measured by changes in UACR (improved from micro- to normo-albuminuria [HR 1.35, 95% CI {1.24, 1.47}], improved from macro- to micro- or normo-albuminuria [HR 1.55, 95% CI {1.34, 1.8}], and decreased deterioration from normo- to micro- or macro-albuminuria [HR 0.84, 95% CI {0.79, 0.89}]).⁴

Farxiga is an inhibitor of SGLT2 indicated as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Farxiga is not approved to reduce the risk of renal or CV death, or to slow the progression of kidney disease.

About DECLARE-TIMI 58

DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI 58 is an AstraZeneca-sponsored, randomised, double-blinded, placebo-controlled, multicentre trial designed to evaluate the effect of Farxiga compared with placebo on CV outcomes in adults with T2D at risk of CV events, including patients with multiple CV risk factors or established CV disease. DECLARE included more than 17,000 patients across 882 sites in 33 countries and was independently run in collaboration with academic investigators from the TIMI study group (Boston, USA) and the Hadassah Hebrew University Medical Center (Jerusalem, Israel).

About DapaCare

DECLARE is part of the extensive DapaCare clinical programme for Farxiga, which will enrol patients in randomised clinical trials including a wide range of mechanistic trials and is supported by a multinational real-world evidence study (CVD-REAL). The DapaCare clinical programme will generate data across a spectrum of people with CV risk factors, established CV disease and varying stages of renal disease, both with and without T2D. DECLARE is paving the way for three Phase III trials: Dapa-HF, DELIVER, Dapa-CKD and DETERMINE. Farxiga is not indicated to reduce the risk of CV events, CV death, or hHF, or the treatment of CKD.

About Farxiga

Farxiga (dapagliflozin) is a first-in-class, oral once-daily selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2) indicated as both monotherapy and as part of combination therapy to improve glycaemic control, with the additional benefits of weight loss and blood pressure reduction, as an adjunct to diet and exercise in adults with T2D. Farxiga has a robust clinical trial programme of more than 35 completed and ongoing Phase IIb/III trials in over 35,000 patients, as well as more than 1.8 million patient-years’ experience.

About AstraZeneca in CV, Renal & Metabolism (CVRM)

CV, renal and metabolism together form one of AstraZeneca’s main therapy areas and 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. Our 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.

About AstraZeneca

AstraZeneca 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. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit astrazeneca.com and follow us on Twitter @AstraZeneca.

References

^{1. Mosenzon O et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: Analysis from DECLARE-TIMI 58 trial. The Lancet Diabetes & Endocrinology.}

^{2. Narres M et al. The Incidence of End-Stage Renal Disease in the Diabetic (Compared to the Non-Diabetic) Population: A Systematic Review. PLoS ONE 2016; 11(1):e0147329.}

^{3. Koye DN et al. The Global Epidemiology of Diabetes and Kidney Disease. Adv Chronic Kidney Dis. 2018; 25(2):121-132.}

^{4. Mosenzon O et al. Effects of dapagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes: a predefined analysis from the DECLARE-TIMI 58 randomised, placebo-controlled trial. Oral Presentation at the American Diabetes Association 79th Scientific Sessions. (Oral 244-OR, Monday, June 10; 8:15 – 8:30 AM PST)}