WILMINGTON, Del.–(BUSINESS WIRE)–High-level results from FARXIGA®’s (dapagliflozin) Phase III DAPA-CKD trial showed a statistically significant and clinically meaningful effect on its primary endpoint of a composite of worsening of renal function or risk of death (defined as a composite endpoint of ≥50% sustained decline in estimated glomerular filtration rate (eGFR), onset of end stage kidney disease (ESKD) or cardiovascular (CV) or renal death) in adult patients with chronic kidney disease (CKD). The trial also met all its secondary endpoints in CKD patients with and without type 2 diabetes (T2D), making FARXIGA the first medicine to significantly reduce the risk of death from any cause in this patient population.
CKD is a serious, progressive condition defined by decreased kidney function affecting nearly 700 million people worldwide, many of them still undiagnosed. Currently there are limited treatment options for these patients. CKD is associated with significant patient morbidity and an increased risk of CV events, such as heart failure (HF) and premature death.
The co-chairs of the trial and its Executive Committee Prof. David Wheeler, University College London, and Prof. Hiddo L. Heerspink, University Medical Center Groningen, said: “The DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment option for patients with chronic kidney disease. The data will be transformative for these patients.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “DAPA-CKD is the first trial to demonstrate overwhelming efficacy, including improvement on survival, in chronic kidney disease patients both with and without type 2 diabetes. We look forward to sharing these exciting FARXIGA results with the scientific community and health authorities worldwide.”
The safety and tolerability profile for FARXIGA was consistent with the well-established safety profile of the medicine.
The full DAPA-CKD trial results will be submitted for presentation at a forthcoming medical meeting.
In March 2020, AstraZeneca announced that the DAPA-CKD trial was being stopped early following a recommendation from an independent Data Monitoring Committee based on its determination of overwhelming efficacy.
Additionally, in May 2020, FARXIGA was approved in the US to reduce the risk of CV death and hospitalization for heart failure (hHF) in adults with HF (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D. FARXIGA is also under review with the European Medicines Agency (EMA), as well as in other regions, for the treatment of patients with HF.
FARXIGA is also indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D, and in the US it is approved to reduce the risk of hospitalization for HF in adults with T2D and established CV disease or multiple CV risk factors. FARXIGA is not indicated to reduce the worsening of renal function or death in patients with CKD.
INDICATIONS AND LIMITATIONS OF USE for FARXIGA® (dapagliflozin)
FARXIGA is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors
- to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction
FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5 mg and 10 mg tablets
- Prior serious hypersensitivity reaction to FARXIGA
- Patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) being treated for glycemic control without established CV disease or multiple CV risk factors
- Patients on dialysis
Warnings and Precautions
- Volume Depletion: FARXIGA can cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating FARXIGA in these patients, assess volume status and renal function. After initiating therapy, monitor for signs and symptoms of hypotension and renal function
- Ketoacidosis in Diabetes Mellitus has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
- Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
- Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
- Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Rare but serious, life-threatening cases have been reported in patients with diabetes mellitus receiving SGLT2 inhibitors including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA
- Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).
Use in Specific Populations
- Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters
- Lactation: FARXIGA is not recommended when breastfeeding
- To improve glycemic control in patients with T2D, the recommended starting dose of FARXIGA is 5 mg orally once daily, taken in the morning. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose can be increased to 10 mg once daily
- To reduce the risk of hospitalization for heart failure in patients with T2D and established CV disease or multiple CV risk factors, the recommended dose of FARXIGA is 10 mg orally once daily
- To reduce the risk of CV death and hospitalization for heart failure in patients with HFrEF, the recommended dose of FARXIGA is 10 mg orally once daily
Chronic kidney disease
CKD can be a serious, progressive condition defined by decreased kidney function (shown by reduced eGFR or markers of kidney damage, or both, for at least three months). The most common causes of CKD are diabetes, hypertension and glomerulonephritis. In its most severe form, known as ESKD, kidney damage and deterioration of kidney function have progressed to the stage where dialysis or kidney transplantation are required. The majority of patients with CKD will die from CV causes before reaching ESKD.
DAPA-CKD is an international, multi-center, randomized, double-blinded trial in 4,304 patients designed to evaluate the efficacy of FARXIGA 10mg, compared with placebo, in patients with CKD Stages 2–4 and elevated urinary albumin excretion, with and without T2D. FARXIGA is given once daily in addition to standard of care. The primary composite endpoint is worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of ESKD and death from CV or renal cause). The secondary endpoints included the time to first occurrence of the renal composite (sustained ≥50% eGFR decline, ESKD and renal death), the composite of CV death or hHF, and death from any cause. The trial was conducted in 21 countries.
AstraZeneca in CV, Renal & Metabolism (CVMD)
CV, renal and metabolism together form one of AstraZeneca’s main therapy areas and 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 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 CVMD 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization 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-us.com and follow us on Twitter @AstraZenecaUS.