Bydureon EXSCEL trial demonstrates favourable cardiovascular (CV) safety profile and fewer CV events in patients with type-2 diabetes at wide range of CV risk

Largest and most inclusive patient population of any GLP-1 CV outcomes trial with 14,500 patients at 687 trial sites across 35 countries

Full trial results presented at the annual meeting of the European Association for the Study of Diabetes (EASD) and simultaneously published in the
New England Journal of Medicine

14 September 2017

AstraZeneca today announced full results from the EXSCEL (EXenatide Study of Cardiovascular Event Lowering) trial that showed cardiovascular safety with Bydureon (exenatide extended-release) in patients with type-2 diabetes (T2D) at a wide range of CV risk.

Exenatide once-weekly did not increase the incidence of major adverse cardiovascular events (MACE), a composite endpoint of CV death, non-fatal heart attack (myocardial infarction) or non-fatal stroke, compared to placebo (Hazard Ratio [HR]: 0.91; 95% Confidence Interval [CI]: 0.83-1.00; p<0.001 for non-inferiority).

There were also fewer CV events observed in the exenatide arm of the trial (839 [11.4%] versus 905 [12.2%]), although the primary efficacy objective of a superior reduction in MACE narrowly missed statistical significance (p=0.061). The direction of the cardiovascular outcomes results in EXSCEL was consistent with those seen in recently completed outcomes trials within the GLP-1 receptor agonist class.¹ Additionally, in a prespecified secondary analysis, patients on exenatide had a 14% lower incidence of death from all causes (HR: 0.86; 95% CI: 0.77-0.97).

The full results of EXSCEL, including important secondary endpoints, sensitivity analyses and regional data, were presented at the 53rd annual meeting of EASD and simultaneously published today online in the New England Journal of Medicine.

Investigator Rury Holman, Professor of Diabetic Medicine and Diabetes Trials Unit Director, University of Oxford, UK, said: “People with type-2 diabetes have up to a two-times increased risk for all-cause mortality and four-times increased risk for cardiovascular death compared to the general population, making it imperative that their type-2 medication does not further increase their risk for cardiovascular disease and related complications.^2,3,4 The EXSCEL study results demonstrated that exenatide could be used safely in patients with type-2 diabetes with a wide range of cardiovascular risk and suggested a potential benefit with respect to all-cause mortality.”

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, said: “The results from the EXSCEL trial provide important evidence supporting the use of once-weekly Bydureon in a broad population of patients with type-2 diabetes at a wide range of cardiovascular risk. This comprehensive trial is representative of our commitment to address multiple risk factors or co-morbidities associated with cardiovascular and metabolic diseases and helps to inform clinical practice for the benefit of millions of patients with type-2 diabetes.”

Multiple sensitivity analyses for MACE, recalculating the outcome under alternative assumptions to determine the potential impact of different variables, were consistent with primary analyses.¹ No safety issues were identified during the EXSCEL trial and data were consistent with the known safety profile of exenatide.¹ Specifically, there was no imbalance in retinopathy, a microvascular complication that commonly occurs from type-2 diabetes and can lead to serious visual disability and blindness.

The EXSCEL trial enrolled the largest and most inclusive patient population of any CV outcomes trial of the glucagon-like peptide-1 (GLP-1) receptor agonist class conducted to date, having included more than 14,500 patients at 687 trial sites across 35 countries, incorporating usual care and wide-ranging eligibility criteria.^1,5,6,7

AstraZeneca is working with regulatory authorities to incorporate these data into the Bydureon label.

NOTES TO EDITORS

About EXSCEL

EXSCEL is a Phase IIIb/IV, double-blind, placebo-controlled, global CV outcomes trial conducted in 35 countries and enrolled 14,500 patients with type-2 diabetes with or without additional CV risk factors or prior CV events. Overall, 73% of included patients had experienced at least one prior CV event, whereas 27% had not. Participants were randomised to receive exenatide once-weekly 2mg or matching placebo by subcutaneous injections. EXSCEL was run jointly by two academic research organisations - the Duke Clinical Research Institute (Durham, NC, US) and the University of Oxford Diabetes Trials Unit (Oxford, UK).

About AstraZeneca in Diabetes

AstraZeneca is pushing the boundaries of science with the goal of developing life-changing medicines that aim to reduce the global burden and complications of diabetes. As a main therapy area for the company, we are focusing our research and development efforts on diverse populations and patients with significant co-morbidities, such as cardiovascular disease, obesity, non-alcoholic steatohepatitis (NASH), and chronic kidney disease.

Our commitment to diabetes is exemplified by the depth and breadth of our global clinical research programme. This commitment is advancing understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination products to help more patients achieve treatment success earlier in their disease.

About AstraZeneca in Cardiovascular, Renal & Metabolic Diseases (CVMD)

Cardiovascular, renal and metabolic diseases together form one of AstraZeneca’s main therapy areas and platforms for future growth. By following the science to understand more clearly the underlying links between the heart, kidney 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 CVMDs and even regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CVMD 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 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.

References

1. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type-2 Diabetes. N Engl J Med. Available at www.nejm.org/doi/full/10.1056//NEJMoa16129. Accessed September 2017.

2.     Tancredi M, et al. Excess mortality among persons with type 2 diabetes. N Engl J Med. 2015;373:1720-32.

3.     National Centers for Disease Control and Prevention. National diabetes statistics report, 2014. Available at https://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Accessed August 9, 2017.

4.     Sarwar N, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215-22.

5.     Marso SP, et al. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. Am Heart J. 2013;166(5):823-830.e5.

6.     Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016; 375:1834-1844.

7.     Pfeffer MA, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med. 2015; 373:2247-2257.

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