FARXIGA Approved in the US for the Treatment of Chronic Kidney Disease in Patients at Risk of Progression With and Without Type 2 Diabetes

AstraZeneca’s FARXIGA^® (dapagliflozin), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been approved in the US to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease (ESKD), cardiovascular (CV) death and hospitalization for heart failure (hHF) in adults with chronic kidney disease (CKD) at risk of progression.

The approval by the Food and Drug Administration (FDA) was based on positive results from the DAPA-CKD Phase III trial. The decision follows the Priority Review designation granted by the FDA earlier this year.

CKD, a condition defined by decreased kidney function, is often associated with a heightened risk of heart disease or stroke, or the need for dialysis or kidney transplant.^1-3 CKD is expected to become the fifth leading cause of mortality globally by 2040.⁴ Currently in the US, 37 million people are estimated to have CKD.¹

The co-chair of the DAPA-CKD trial and its executive committee, Prof. Hiddo L. Heerspink, University Medical Center Groningen, the Netherlands, said: “Based on the unprecedented results of the DAPA-CKD trial, dapagliflozin is now the first SGLT2 inhibitor approved for the treatment of chronic kidney disease regardless of diabetes status. This transformational milestone provides patients and physicians with a new and effective treatment option for this often debilitating and life-threatening disease.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Today’s approval is the most significant advancement in the treatment of chronic kidney disease in more than 20 years. We’ve shown impressive efficacy for FARXIGA in type 2 diabetes, heart failure with reduced ejection fraction and, most recently, chronic kidney disease and we are thrilled to be able to bring this medicine to millions of patients in the US.”

The DAPA-CKD trial demonstrated that FARXIGA, on top of standard-of-care treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, reduced the relative risk of worsening of renal function, onset of ESKD, or risk of CV or renal death by 39%, the primary composite endpoint, compared to placebo (p<0.0001) in patients with CKD Stages 2-4 and elevated urinary albumin excretion. The absolute risk reduction (ARR) was 5.3% over the median time in study of 2.4 years. FARXIGA also significantly reduced the relative risk of death from any cause by 31% (ARR=2.1%, p=0.0035) compared to placebo.⁵

Exploratory analyses of the DECLARE-TIMI 58 Phase III trial, a randomized, double-blind, placebo-controlled trial, conducted to determine the effect of FARXIGA on CV outcomes support the conclusion that FARXIGA is also likely to be effective in patients with less advanced CKD. FARXIGA is not recommended for the treatment of CKD in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease, since it is not expected to be effective in these populations.

In both trials, the safety and tolerability of FARXIGA were consistent with the well-established safety profile of the medicine.

In the US, FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D), and to reduce the risk of hHF in adults with T2D and established CV disease or multiple CV risk factors. FARXIGA is also indicated to reduce the risk of CV death and hHF in adults with heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D.

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 either 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
• to reduce the risk of sustained eGFR decline, end‑stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression

FARXIGA is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

FARXIGA is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m². FARXIGA is likely to be ineffective in this setting based upon its mechanism of action.

FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. FARXIGA is not expected to be effective in these populations.

IMPORTANT SAFETY INFORMATION for FARXIGA

Contraindications

• Prior serious hypersensitivity reaction to FARXIGA
• Patients on dialysis

Warnings and Precautions

• Ketoacidosis in Diabetes Mellitus has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis