Astrazeneca Regulatory News (AZN)

28 June 2021 07:05 BST

Forxiga recommended for approval in the EU by CHMPfor the treatment of patients with chronic kidney disease

If approved, Forxiga has the potential to change the treatment paradigmfor millions of people in the EU suffering from chronic kidney disease

AstraZeneca's Forxiga (dapagliflozin) has been recommended for approval in the European Union (EU) for the treatment of chronic kidney disease (CKD) in adults with and without type-2 diabetes (T2D).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the DAPA-CKD Phase III trial that showed Forxiga, on top of standard-of-care treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, reduced the risk of the composite of worsening of renal function, end-stage kidney disease (ESKD) and cardiovascular (CV) or renal death, compared to placebo.

Forxiga also significantly reduced the risk of death from any cause, compared to placebo. In the trial, the safety and tolerability of Forxiga were consistent with the well-established safety profile of the medicine.

CKD is a serious, progressive condition defined by decreased kidney function and is often associated with an increased risk of heart disease or stroke.1-3 It affects approximately 47 million people in the EU and nearly 840 million people worldwide.3,4 However, diagnosis rates remain low and up to 90% of patients are unaware they have the disease.5

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "The unprecedented results of the DAPA-CKD Phase III trial show that Forxiga can significantly slow the decline of kidney function and reduce the risk of death for patients with chronic kidney disease. This positive CHMP opinion underscores Forxiga's potential to transform the future care of chronic kidney disease and brings us one step closer to providing a much-needed new treatment option to millions of patients in the EU."

Forxiga (known as Farxiga in the US) was recently approved in the US for the treatment of CKD in adults with and without T2D and, in addition to the EU, is currently under review in Japan and other countries around the world. Forxiga is also indicated as an adjunct to diet and exercise to improve glycaemic control in adults with T2D and for the treatment of symptomatic chronic heart failure (HF) with reduced ejection fraction (HFrEF) in adults with and without T2D.

CKD

CKD is a serious, progressive condition defined by decreased kidney function (shown by reduced estimated glomerular filtration rate (eGFR) or markers of kidney damage, or both, for at least three months).3 The most common causes of CKD are diabetes, hypertension and glomerulonephritis.6 CKD is associated with significant patient morbidity and an increased risk of CV events, such as HF and premature death. In its most severe form, known as ESKD, kidney damage and deterioration of kidney function have progressed to the point where dialysis or kidney transplantation are required.1 The majority of patients with CKD will die from CV causes before reaching ESKD.7

DAPA-CKD

DAPA-CKD was an international, multi-centre, randomised, double-blinded Phase III trial in 4,304 patients designed to evaluate the efficacy of Forxiga 10mg, compared with placebo, in patients with CKD Stage 2-4 and elevated urinary albumin excretion, with and without T2D. Forxiga was given once daily in addition to standard of care. The primary composite endpoint was worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of ESKD or death from CV or renal cause). The secondary endpoints included the time to first occurrence of the renal composite (sustained ≥50% eGFR decline, ESKD or renal death), the composite of CV death or hospitalisation for HF (hHF), and death from any cause. The trial was conducted in 21 countries.8 Detailed results from the trial were published in The New England Journal of Medicine.8

Forxiga

Forxiga (dapagliflozin) is a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor. The research for Forxiga is advancing from cardiorenal effects to prevention and organ protection as science continues to identify the underlying links between the heart, kidneys and pancreas. Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and CKD.

For nearly a decade Forxiga has been an effective monotherapy and part of combination therapy as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Following results from the landmark DECLARE-TIMI 58 Phase III CV outcomes trial, it is approved in adults with T2D to reduce the risk of hHF or CV death when added to standard of care.9 Forxiga is also the first SGLT2 inhibitor approved for the treatment of HFrEF in adults with and without T2D.

In August 2020, results from the DAPA-CKD Phase III trial demonstrated that Forxiga achieved unprecedented reduction in the composite risk of kidney failure and CV or renal death in patients with CKD with and without T2D versus placebo.8 It is now the first SGLT2 inhibitor approved for the treatment of CKD regardless of diabetes status.

DapaCare is a robust programme of clinical trials to evaluate the potential CV, renal and organ protection benefits of Forxiga. It 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. It is currently being assessed in patients with HF with preserved ejection fraction in the DELIVER Phase III trial. Forxiga is also being tested in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI Phase III trial - a first of its kind, indication-seeking registry-based randomised controlled trial.

AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca's three disease 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 for organ protection and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. 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 CV health for millions of patients worldwide.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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References

1. Centers for Disease Control and Prevention. Chronic kidney disease in the United States, 2021; 2021 [cited 2021 Jun 1]. Available from: URL: https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.html.

2. Segall L, et al. Heart failure in patients with chronic kidney disease: a systematic integrative review. Biomed Res Int. 2014;2014:937398.

3. Bikbov B, et al. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709-733.

4. Jager KJ, et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019;34(11):1803-1805.

5. National Kidney Foundation. Kidney Disease: The Basics; 2021 [cited 2021 Jun 1]. Available from: URL: https://www.kidney.org/news/newsroom/factsheets/KidneyDiseaseBasics.

6. National Kidney Foundation. Kidney Disease: Causes; 2015 [cited 2021 Jun 1]. Available from: URL: https://www.kidney.org/atoz/content/kidneydiscauses.

7. Briasoulis A, Bakris GL. Chronic kidney disease as a coronary artery disease risk equivalent. Curr Cardiol Rep. 2013;15(3):340.

8. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.

9. Wiviott SD, 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.

Adrian Kemp

Company Secretary

AstraZeneca PLC