AstraZeneca presents new data underpinning safety profile and Real-World CV outcomes of Farxiga at ADA 2017

Comprehensive updated analysis provides valuable evidence on the safety profile of Farxiga, including no imbalance in lower-limb amputations

New analyses from CVD-REAL examine reductions in CV events for SGLT-2 inhibitors, including Farxiga in patients with and without CV disease versus DPP-4 inhibitors

AstraZeneca presented new data at the American Diabetes Association’s (ADA) 77th Scientific Sessions underpinning the safety profile of Farxiga (dapagliflozin) with an analysis of data pooled from dapagliflozin clinical trials1, as well as three new cardiovascular (CV) outcomes analyses from the ongoing CVD-REAL study, the first large real-world evidence study of its kind evaluating treatment with SGLT-2 inhibitors (SGLT-2i), including dapagliflozin.2-4

In an updated safety analysis, data pooled from 30 Phase IIb/III clinical trials for dapagliflozin showed no new safety signals and the incidence of adverse events was generally similar to that in the control groups. Importantly, there was no imbalance in lower-limb amputations, with eight (0.1%) patients and seven (0.2%) patients identified in the dapagliflozin and control groups, respectively.[i]

Following the primary publication of the CVD-REAL study in May 2017, three new analyses presented at ADA add to the ongoing evaluation of earlier treatment with SGLT-2is and in broader patient populations with type-2 diabetes (T2D). The analyses evaluated effects in additional real-world patient populations, including CV endpoints specific to dapagliflozin:

• A two-country analysis of more than 30,000 patients with T2D showed a significant reduction in the rates of hospitalisation for kidney disease by 62% (p< 0.001), hospitalisation for heart failure (HF) by 37% (p< 0.001) and death from any cause by 27% (p=0.003) for patients using dapagliflozin versus DPP-4 inhibitors (DPP-4is)[ii]

• A three-country analysis of nearly 100,000 patients with T2D showed a significant reduction in rates of CV death by 47% (p< 0.001) and hospitalisation for HF by 30% (p< 0.001), for patients new to SGLT-2is versus other T2D medicines[iii]

• A late-breaking oral presentation analysing data from more than 300,000 patients across five countries will explore the rates of HF and death in patients with T2D, both with and without CV disease, receiving treatment with SGLT-2is versus other T2D medicines (Oral 377-OR, Tuesday June 13, 10:45am PDT)[iv]

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, said: “SGLT-2 inhibitors are being prescribed with greater frequency for patients with type-2 diabetes, so it is vital that we have a clear understanding of the safety profile of these medicines and examine their effectiveness in a real-world setting. The data we are presenting at ADA underpins the safety of Farxiga and highlights the potential for earlier use of the SGLT-2 inhibitor class, and in broader patient populations than originally understood.”

The CVD-REAL study is ongoing and future analyses will be conducted using this dataset as well as data from additional countries. The data for the study were obtained from anonymised real-world sources including medical records, claims databases and national registries, and were not independently adjudicated or verified against source documents. The analysis was validated by the independent academic statistical group at St. Luke’s Mid America Heart Institute, Kansas City, USA. While CVD-REAL was a large study with a robust propensity-matching technique, given its observational nature the possibility of residual, unmeasured confounding factors cannot be definitively excluded.

Dapagliflozin is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Dapagliflozin is not indicated to reduce the risk of CV events, death or hospitalisation for heart failure. The dapagliflozin cardiovascular outcomes trial, DECLARE, is ongoing and expected to provide data in 2019 at the latest.

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NOTES TO EDITORS

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 dapagliflozin 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. DapaCare underscores our commitment to following the science by pursuing a holistic patient approach to address the multiple risk factors associated with CV, metabolic and renal diseases.

About AstraZeneca in Cardiovascular & Metabolic Diseases (CVMD)

Cardiovascular, renal and metabolic diseases are key areas of focus for AstraZeneca as part of the company’s strategy for achieving scientific leadership and returning to growth. By collaborating across therapeutic disciplines within the CVMD therapy area, we are addressing the underlying disorders that drive CVMD risk, with the goal of reducing morbidity, mortality and organ damage through innovative therapies. Recognising the growing unmet needs and challenges faced by the millions of people worldwide living with these interrelated diseases, we are determined to understand how they interact and impact one another – and how they can be treated together to save more patients’ lives.

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 main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca.

[i] Jabbour, S. et al. “Safety Update on Dapagliflozin (DAPA) Across the Phase 2b/3 Clinical Trial Program.” American Diabetes Association Scientific Sessions 2017. Abstract #1263-P

[ii] Norhammar A. et al. “Dapagliflozin is associated with lower risk of hospitalisation for kidney disease, heart failure and all-cause death compared to DPP-4i: CVD-REAL Nordic.” American Diabetes Association Scientific Sessions 2017. Abstract #165-LB

[iii] Birkeland K. et al. “SGLT-2i is associated with lower risk of mortality and heart failure compared to other glucose lowering drugs: A three-country analysis.” American Diabetes Association Scientific Sessions 2017. Abstract #1205-P

[iv] Cavender M. et al. “Hospitalisation for heart failure and death in new users of SGLT-2 inhibitors in patients with and without cardiovascular disease – CVD-REAL study.” American Diabetes Association Scientific Sessions 2017. Abstract #377-OR