Forxiga reduced the risk of a composite of cardiovascular death or hospitalisation for heart failure in patients with type-2 diabetes, both with and without kidney disease

In a new pre-specified sub-analysis from Phase III DECLARE-TIMI 58 trial, Forxiga showed a 42% relative risk reduction (absolute risk reduction = 8.3%) versus placebo in patients with prominent kidney disease markers
 

AstraZeneca today announced a new pre-specified sub-analysis from the Forxiga (dapagliflozin) Phase III DECLARE-TIMI 58 trial that shows the medicine reduced the relative risk for the composite of cardiovascular (CV) death or hospitalisation for heart failure (hHF) in patients with type-2 diabetes (T2D) at risk of CV events, independent of the status of two prominent kidney disease markers: estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73m² and presence of albuminuria. The analysis also showed Forxiga was non-inferior regarding the occurrence of major adverse cardiovascular events (MACE), independent of these markers.¹

These data were presented today at ESC Congress 2019 in Paris, France.

Elisabeth Björk, Senior Vice President, Head of Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said: “People with diabetes are about twice as likely to develop chronic kidney disease as those without,² and renal dysfunction has been shown to predict cardiovascular outcomes.¹ The DECLARE-TIMI 58 results build on the extensive body of evidence for Forxiga as a treatment for patients with type-2 diabetes who have a high cardiovascular risk, and the data can give physicians confidence in a SGLT2 inhibitor, like Forxiga, to treat this patient population.”

The DECLARE-TIMI 58 trial evaluated 17,160 patients with T2D at risk of CV events, of which 34.5% (5915) had manifestations of chronic kidney disease (CKD): 31.3% (5367) had either an eGFR <60 ml/min/1.73m² or albuminuria ([UACR] ≥ 30mg/g), 3.2% (548) had both manifestations. Patients with a Creatinine-Clearance < 60ml/min at enrolment were excluded from the study.¹ The sub-analysis presented at the ESC Congress 2019 showed that patients with more abnormal markers had higher event rates for CV death/hHF (KM event rates at 4 years of 3.9%, 8.3%, 17.4%) or MACE (7.5%, 11.7%, and 18.9%) for no, one or two markers of CKD, respectively. The relative risk reductions versus placebo for CV death/hHF and MACE were generally consistent across the subgroups (both p-interaction >0.29), though numerically greatest (42%) in patients with both reduced eGFR and albuminuria.¹

Forxiga is an inhibitor of SGLT2 indicated in adults for the treatment of insufficiently controlled T2DM as an adjunct to diet and exercise. Forxiga should not be initiated in patients with a glomerular filtration rate [GFR] < 60 mL/min and should be discontinued at GFR persistently below 45 mL/min. Forxiga has not been studied in severe renal impairment (GFR < 30 mL/min) or end-stage renal disease and is not indicated to reduce the risk of CV events, heart failure or death.³

About DECLARE-TIMI 58

DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI 58 is the largest CV outcomes trial conducted for a selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2) to date in a broad patient population. It is an AstraZeneca-sponsored, Phase III, randomised, double-blinded, placebo-controlled, multicentre trial, designed to evaluate the effect of Forxiga 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 and also assessed key renal secondary endpoints. The trial 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, US) and the Hadassah Hebrew University Medical Center (Jerusalem, Israel).

The full results of the DECLARE-TIMI 58 trial were published in The New England Journal of Medicine in January 2019.

About the DapaCare Clinical Programme

AstraZeneca is taking a holistic, patient-centric approach to disease management by addressing the underlying morbidity, mortality and organ damage associated with cardiovascular (CV), metabolic and renal diseases. Due to the interconnectivity of these diseases, AstraZeneca has developed the DapaCare clinical programme to explore the CV and renal profile of Forxiga in people with and without type-2 diabetes. The clinical programme will enrol nearly 30,000 patients in randomised clinical trials and is supported by a multinational real-world evidence study. DapaCare will generate data across a spectrum of people with established CV disease, CV risk factors and varying stages of renal disease, both with and without type-2 diabetes, providing healthcare providers with evidence needed to improve patient outcomes. Forxiga is also being developed for patients with chronic heart failure in the DELIVER (HFpEF) and DETERMINE (HFrEF and HFpEF) trials, in addition to chronic kidney disease in the DAPA-CKD trial. DapaCare underscores our commitment to following the science by pursuing a holistic patient approach to address the multiple risk factors associated with CV, renal and metabolic diseases.

About Forxiga

Forxiga  is a first-in-class, oral once-daily SGLT2 inhibitor indicated as both monotherapy and as part of combination therapy to treatment of insufficiently controlled type 2 diabetes mellitus , with the additional benefits of weight loss and blood-pressure reduction, as an adjunct to diet and exercise in adults with T2D. Forxiga 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.

About AstraZeneca in CVRM

Cardiovascular, Renal & 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.

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, CVRM, 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.

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References

^{1. Zelniker TA, Raz I, Mosenzon O. Effect of dapagliflozin on cardiovascular outcomes in patients with type 2 diabetes according to baseline renal function and albuminuria status: Insights from DECLARE-TIMI 58 [presented at: European Society of Cardiology (ESC) Congress 2019, Aug 31-Sept 4, Paris, France.].}

^{2. Koye DN et al. The Global Epidemiology of Diabetes and Kidney Disease. Adv Chronic Kidney Dis 2018; 25(2):121–32.}

^{3. European Medicines Agency. Summary of Product Characteristics: Forxiga; 2012. Available from: URL: https://www.ema.europa.eu/en/documents/product-information/forxiga-epar-product-information_en.pdf.}