October 21, 2019 – AstraZeneca today announced that the U.S. Food and Drug Administration (FDA) has approved FARXIGA (dapagliflozin) to reduce the risk of hospitalization for heart failure (hHF) in adults with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or multiple cardiovascular (CV) risk factors.
The approval is based on results from the landmark DECLARE-TIMI 58 CV outcomes trial (CVOT), the largest sodium-glucose cotransporter 2 (SGLT2) inhibitor CVOT conducted to date to evaluate T2D patients with multiple CV risk factors or established CV disease.
Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, said: “FARXIGA is the first SGLT2 inhibitor approved in the US to reduce the risk of hospitalization for heart failure in type 2 diabetes patients with established cardiovascular disease or multiple cardiovascular risk factors. This is promising news for the 30 million people living with type 2 diabetes in the US, as heart failure is one of the earliest cardiovascular complications for them, before heart attack or stroke. FARXIGA now offers the opportunity for physicians to act sooner and reduce the risk of hospitalization for heart failure.”
Dr. Stephen Wiviott of Brigham and Women’s Hospital and Harvard Medical School, Boston, and a Senior Investigator with the TIMI study group and co-principal investigator of the trial, said: “DECLARE-TIMI 58 is a landmark trial, offering compelling evidence that dapagliflozin can reduce the risk of heart failure in patients living with type 2 diabetes with multiple risk factors for or established cardiovascular disease. These data could help change the way we approach diabetes management – going beyond a singular focus on glucose control to help address the risk of heart failure in a diverse population of patients.”
Today’s FDA approval follows the update to the marketing authorization in the EU in August 2019. FARXIGA is also under regulatory review in China with a decision anticipated in the first half of 2020.
The FDA has granted Fast Track designation for FARXIGA to reduce the risk of CV death, or the worsening of heart failure in adults with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) based on the Phase III trials, DAPA-HF and DELIVER, and Fast Track designation to delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease (CKD) based on the Phase III DAPA-CKD trial. FARXIGA is not indicated to reduce the risk of heart failure, CV death or kidney disease.
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.
Please see accompanying US Full Prescribing Information and Medication Guide for FARXIGA.
About DECLARE-TIMI 58
DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI 58 is the largest CV outcomes trial conducted for a selective inhibitor of SGLT2 to date in a broad patient population. It is an AstraZeneca-sponsored, Phase III, randomized, double-blind, placebo-controlled, multicenter trial designed to evaluate the effect of FARXIGA compared with placebo on CV outcomes in adults with T2D at risk of CV events, including patients with multiple CV risk factors or established CV disease and also assessed key renal secondary endpoints. The trial included more than 17,000 patients across 882 sites in 33 countries and was independently run in collaboration with academic investigators from the TIMI study group (Boston, US) and the Hadassah Hebrew University Medical Center (Jerusalem, Israel).
DECLARE-TIMI 58 showed that FARXIGA significantly reduced the risk of the primary composite endpoint of hHF or CV death versus placebo by 17% (4.9% vs. 5.8%; HR 0.83 [95% CI 0.73-0.95], p=0.005). This finding was driven by a significant 27% reduction in the risk of hHF (2.5% vs. 3.3%; HR 0.73 [95% CI 0.61, 0.88]). The treatment benefit was consistent across patient subgroups. The Phase III DECLARE-TIMI 58 trial confirmed the well-established safety profile of FARXIGA.
The full results of the DECLARE-TIMI 58 trial were published in The New England Journal of Medicine in January 2019.
About 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.