January 6, 2020 — AstraZeneca today announced the US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) and granted Priority Review for FARXIGA® (dapagliflozin) to reduce the risk of cardiovascular (CV) death or the worsening of heart failure (HF) in adults with heart failure with reduced ejection fraction (HFrEF) with and without type 2 diabetes (T2D).
The Prescription Drug User Fee Act date, the FDA action date for this supplemental application, is scheduled for the second quarter of 2020.
The sNDA was based on results from the landmark Phase III DAPA-HF trial published in September 2019 in The New England Journal of Medicine, which showed FARXIGA on top of standard of care reduced the incidence of the composite outcome of CV death or the worsening of HF versus placebo. FARXIGA is not indicated to reduce the risk of hospitalization for heart failure (hHF) in patients without diabetes, or to reduce the risk of CV death.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “FARXIGA is well established in the treatment of type 2 diabetes and this Priority Review shows its potential to also impact millions of patients with heart failure. If approved, FARXIGA will be the first and only medicine of its kind indicated to treat patients with heart failure.”
In September 2019, the FDA granted Fast Track designation for the development of FARXIGA in HF. In August 2019, the FDA also granted Fast Track designation for the development of FARXIGA to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease, with and without T2D.
FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D. In October 2019, the FDA also approved FARXIGA to reduce the risk of hospitalization for heart failure in patients with T2D and established cardiovascular disease or multiple CV risk factors.
Indication and Limitations of Use for FARXIGA® (dapagliflozin) tablets
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 disease or multiple cardiovascular risk factors
FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Important Safety Information for FARXIGA® (dapagliflozin) tablets
- Prior serious hypersensitivity reaction to FARXIGA
- Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
Warnings and Precautions
- Hypotension: FARXIGA causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating FARXIGA in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension
- Ketoacidosis 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
- Acute Kidney Injury: FARXIGA causes intravascular volume contraction and can cause acute kidney injury. Reports of acute kidney injury requiring hospitalization and dialysis have occurred with FARXIGA. If acute kidney injury occurs, discontinue and promptly treat
Increases in serum creatinine and decreases in eGFR may be observed with initiation of FARXIGA. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses
Before initiating FARXIGA, evaluate renal function and monitor periodically. FARXIGA is not recommended when the eGFR is <45 mL/min/1.73 m2
- 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 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.