AstraZeneca and Saint Luke’s Mid America Heart Institute initiate Phase III DARE-19 trial with Farxiga in COVID-19 patients

AstraZenecaAstraZeneca and Saint Luke's Mid America Heart Institute have initiated a randomised, global Phase III trial to assess the potential of Farxiga (dapagliflozin) as a treatment in patients hospitalised with COVID-19 who are at risk of developing serious complications, such as organ failure.

The goal of the trial, called DARE-19, is to assess whether Farxiga, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, can reduce the risk of disease progression, clinical complications, and death due to COVID-19 in patients who also have cardiovascular (CV), metabolic or kidney risk factors.

Cardiac, renal and metabolic comorbidities have been associated with poor outcomes and death in COVID-19 patients. The trial design is supported by extensive data on the protective effect of Farxiga in patients with heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD) or type 2 diabetes (T2D).(1-5)

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "AstraZeneca is committed to finding new solutions to fight COVID-19 by investigating the application of our new and existing medicines. With the Phase III DARE-19 trial, we aim to test whether Farxiga can prevent serious complications such as organ failure in those patients with pre-existing health conditions, a critical goal when treating COVID-19."

Mikhail N. Kosiborod, M.D., cardiologist at Saint Luke's Mid America Heart Institute, Vice President of Research at Saint Luke's Health System, and principal investigator of DARE-19 said: "Dapagliflozin has demonstrated cardio and renal protective benefits and improved outcomes in high-risk patients with type-2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease. Patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications. Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory and kidney decompensation, which are common in patients with COVID-19."

The DARE-19 trial is open for enrolment in the US and other European countries with a high COVID-19 burden and aims to recruit approximately 900 patients.

About DARE-19

DARE-19 is an international, parallel-group, randomised, double-blind, placebo-controlled, investigator-sponsored Phase III trial evaluating the efficacy and safety of Farxiga in addition to background local standard of care therapy, on the risk of all-cause death or disease progression and complications in adults who are hospitalised with COVID-19 at the time of trial enrolment. Patients enrolled in DARE-19 also have a medical history of hypertension (HTN), atherosclerotic CV disease, heart failure with reduced or preserved ejection fraction, T2D or CKD Stage III to IV. The primary efficacy outcome of the trial is time to first occurrence of death from any cause or new/worsened organ dysfunction through 30 days of follow-up.

Some of the patients at highest risk of COVID-19 complications appear to be those with cardiometabolic disease.(6,7,8) CV complications, including acute myocardial injury and heart failure (HF) are common in COVID-19, and appear to be key drivers of poor outcomes and death especially in patients with pre-existing CV disease and/or CKD. (9,10)

About COVID-19 and AstraZeneca Research

AstraZeneca is rapidly mobilising its COVID-19 research efforts to focus on key areas: identifying novel coronavirus-neutralising antibodies against the SARS-CoV-2 virus to prevent or treat disease progression; and investigating the application of our new and existing medicines to suppress the body’s overactive immune response, or protect from serious complications, such as organ failure caused by COVID-19 disease.

About Farxiga

Farxiga is a first-in-class, oral, once-daily SGLT2 inhibitor indicated in adults for the treatment of insufficiently controlled T2D as both monotherapy and as part of combination therapy as an adjunct to diet and exercise to improve glycaemic control, with the additional benefits of weight loss and blood-pressure reduction. In the DECLARE CV outcomes trial in adults with T2D, Farxiga reduced the risk of the composite endpoint of hospitalisation for HF or CV death versus placebo, when added to standard of care.

About AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) 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 and Metabolism, and Respiratory. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

1. Wiviott SD, Raz I, Bonaca MP, et al, for the DECLARE-TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [article and supplementary appendix]. N Engl J Med. 2019:380:347-357.
2. McMurray JJV, Solomon SD, Inzucchi SE, et al, on behalf of the DAPA-HF Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction [article, online protocol, and supplementary appendix]. N Engl J Med. 2019;318;1995-2008.
3. Solomon SD, Jhund P, Kosiborod MN, et al. Effect of dapagliflozin on renal function in heart failure with reduced ejection fraction: the DAPA-HF Trial [presentation]. Presented at American Society of Nephrology Kidney Week; November 5-10, 2019; Washington, DC.
4. AstraZeneca Pharmaceuticals LP. Farxiga Phase III DAPA-CKD trial will be stopped early after overwhelming efficacy in patients with chronic kidney disease [press release]. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/farxiga-phase-iii-dapa-ckd-trial-will-be-stopped-early-after-overwhelming-efficacy-in-patients-with-chronic-kidney-disease.html. Published March 30, 2020. Accessed April 7, 2020.
5. Sabatine MS, DeMets DL, Inzucchi SE, et al. Timing of onset of clinical benefit with dapagliflozin in patients with heart failure: an analysis from DAPA-HF [presentation]. Presented at: American Heart Association Scientific Sessions; November 16-18, 2019; Philadelphia, PA.
6. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State [published online ahead of print March 19, 2020]. JAMA. 2020.
7. Center for Disease Control. Coronavirus Disease 2019 (COVID-19): interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). Website. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html. Accessed April 2, 2020.
8. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention [published online ahead of print February 24, 2020]. JAMA. 2020.
9. Madjid M, Safavi-Naeini P, Solomon SD, et al. Potential effects of coronaviruses on the cardiovascular system: a review [published online ahead of print March 27, 2020]. JAMA Cardiol. 2020. http://dx.doi.org/10.1001/jamacardio.2020.1286. Accessed April 2, 2020.
10. Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020. http://dx.doi.org/10.1016/j.kint.2020.03.005. Accessed April 3, 2020.

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