AstraZeneca expands heart failure research with new Phase III DELIVER trial of Forxiga in patients with and without type-2 diabetes

The latest Phase III outcomes trial added to the global DapaCare clinical programme

Enrolment closes for Phase III DAPA-HF trial, the first trial to assess the potential cardiovascular benefits of an SGLT-2 
inhibitor in patients with and without type-2 diabetes

23 August 2018
 

AstraZeneca today announced two updates to its global heart failure (HF) research programme for Forxiga (dapagliflozin), a selective sodium-glucose co-transporter-2 inhibitor (SGLT-2i) currently approved for the treatment of type-2 diabetes (T2D).

Despite advances in healthcare, HF remains as life-threatening and prevalent as the combined incidence of the four most commons forms of malignancy.¹ There were an estimated 63.6 million cases of HF worldwide in 2016, and 50 percent of patients will die within five years of diagnosis.^1,2  In the same year, there were approximately 7.78 million patient years of disability due to HF, resulting in significant costs to healthcare systems and society through morbidity, unpaid care costs, premature death and lost productivity.¹

DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients with PReserved Ejection Fraction Heart Failure) is an international, double-blind, randomised, placebo-controlled Phase III trial evaluating the effects of Forxiga on reducing cardiovascular (CV) death or worsening HF in patients with HF and a preserved ejection fraction (HFpEF), a condition where the heart muscle contracts normally but the ventricles do not relax as they should, resulting in a decreased total amount of blood pumped throughout the body.³ DELIVER is the latest outcomes study added to AstraZeneca’s global DapaCare clinical programme exploring the CV and renal profile of Forxiga across a spectrum of people, both with and without T2D, who have CV risk factors, established CV disease and varying stages of renal disease.⁵

Dr. Scott Solomon, Professor of Medicine at Harvard Medical School and Brigham and Women’s Hospital and chair of the DELIVER trial, said: “Heart failure with preserved ejection fraction accounts for about half the hospital admissions for heart failure.⁴ The prevalence is rising as the population ages, and there is currently no evidence-based therapy. DELIVER will test whether Forxiga can reduce morbidity and mortality in this population for which there is substantial unmet need.”

DELIVER is a complementary trial to DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure), an international, double-blind, randomised, placebo-controlled Phase III trial, evaluating the effects of dapagliflozin on CV death or worsening HF in patients with HF and reduced ejection fraction (HFrEF), a condition where the heart muscle does not contract effectively and less oxygen-rich blood is pumped out to the body.³ DAPA-HF is the first trial to assess the potential CV benefits of an SGLT-2i in patients with and without T2D and, with enrolment completed, is on track for completion in 2019.⁶

Dr. John McMurray, Professor of Medical Cardiology, University of Glasgow, Chairman of the Executive Committee for DAPA-HF and member of the Executive Committee for DELIVER, said: “This partnership between AstraZeneca and the wider clinical community has enabled us to test the efficacy and safety of Forxiga across the spectrum of heart failure. The results may ultimately transform the way we view and manage a condition that has afflicted millions of patients and placed a huge burden on our health care systems worldwide.”

Elisabeth Bjork, Vice President, Head of Cardiovascular, Renal and Metabolism, Global Medicines Development at AstraZeneca, said: “Through DAPA-HF and DELIVER, alongside DECLARE, we are pushing the boundaries of science in HF research for this class of medicine, both in type-2 diabetes and beyond. It is our mission to improve patient outcomes for these highly prevalent diseases by advancing clinical understanding in cardiovascular, renal and metabolic diseases with Forxiga, for which the body of scientific evidence continues to grow through a robust clinical programme of more than 35 completed and ongoing Phase IIb/III trials in over 35,000 patients.”

NOTES TO EDITORS

About Forxiga (dapagliflozin)

Forxiga is a first-in-class, oral, once-daily selective inhibitor of human sodium-glucose co-transporter 2 (SGLT-2i) 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. Forxiga is not indicated to reduce the risk of CV events, death or hHF.

Forxiga has a robust clinical trial programme of more than 35 completed and ongoing Phase 2b/3 trials in over 35,000 patients. With more than 1.8 million patient-years’ experience and 300,000 prescriptions written to-date, Forxiga has achieved blockbuster status as the most prescribed SGLT-2i.

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 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. 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 AstraZeneca in Cardiovascular, Renal & Metabolism (CVRM)

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 CVRM diseases and even 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, 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 www.astrazeneca.com and follow us on Twitter @AstraZeneca. 

References

1.     GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211-1259.

2.     Roger V, et al.; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics–2012 Update. Circulation. 2012; 125: e2-e220.

3.     “Ejection Fraction Heart Failure Measurement”. Heart.org. Accessed 22 August 2018.

https://www.heart.org/en/health-topics/heart-failure/diagnosing-heart-failure/ejection-fraction-heart-failure-measurement

4.     J. Roy, et. al. “Ventricular Arrhythmias in Heart Failure”. Cardiac Electrophysiology: From Cell to Bedside, 2014 (6); Accessed 22 August 2018.

doi: https://doi.org/10.1016/B978-1-4557-2856-5.00089-3

5.     National Institutes of Health. Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure. (DELIVER). NCT03619213. Accessed 13 August 2018. [https://clinicaltrials.gov/ct2/show/NCT03619213?term=dapagliflozin&cond=Heart+Failure+with+Preserved+Ejection+Fraction&rank=1#wrapper]

6.     AstraZeneca.  Study to evaluate the effect of dapagliflozin on the incidence of worsening heart failure or cardiovascular death in patients with chronic heart failure (DAPA-HF). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT03036124. Accessed August 6, 2018.