FARXIGA reduced the incidence of heart failure worsening or cardiovascular death in a sub-analysis from landmark Phase III DAPA-HF trial

New data from a sub-analysis of the landmark Phase III DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial showed that AstraZeneca's FARXIGA (dapagliflozin) reduced the incidence of the primary composite endpoint of heart failure (HF) worsening or cardiovascular (CV) death compared to placebo, in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of their background therapy (i.e. other medications for heart failure).

FARXIGA was evaluated in patients who were receiving a broad range of pharmacological treatments, device therapies and cardiac resynchronization therapy for HFrEF. A consistent reduction in the primary outcome was observed across all these treatment subgroups.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "These new data from the DAPA-HF trial further reinforce FARXIGA's clinical effects beyond diabetes. By reducing the risk of heart failure worsening regardless of background therapy, FARXIGA has the potential to improve current standard of care and reduce the burden of disease for heart failure patients across the globe."

The results were made available at the American College of Cardiology's 69^th Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC) and were published in the European Heart Journal.

FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D. In the US it is also approved to reduce the risk of hospitalization for HF in patients with T2D and established CV disease or multiple CV risk factors.

In January 2020, the US Food and Drug Administration (FDA) accepted a supplemental New Drug Application (sNDA) and granted Priority Review for FARXIGA to reduce the risk of CV death or the worsening of HF in adults with HFrEF with and without T2D. The Prescription Drug User Fee Act date, the FDA action date for this supplemental application, is scheduled for the second quarter of 2020.

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

Contraindications

• 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

Adverse Reactions

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.

Dosing

• To improve glycemic control in patients with T2D, the recommended starting dose of FARXIGA is 5 mg 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, the recommended dose of FARXIGA is 10 mg once daily.

Please see accompanying US Full Prescribing Information and Medication Guide for FARXIGA.

Notes

Heart failure

HF is a life-threatening disease in which the heart cannot pump enough blood around the body. It affects approximately 64 million people worldwide, at least half of whom have a reduced ejection fraction, and is a chronic and degenerative disease where half of patients will die within five years of diagnosis. HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancers). It is the leading cause of hospitalization for those over the age of 65 and represents a significant clinical and economic burden.

DAPA-HF

DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) is an international, multicenter, parallel-group, randomized, double-blinded trial in patients with heart failure and reduced ejection fraction (LVEF ? 40%), with and without T2D, designed to evaluate the effect of FARXIGA 10mg, compared with placebo, given once daily in addition to standard of care. The primary composite endpoint was time to the first occurrence of a worsening heart failure event (hospitalization or equivalent event; i.e. an urgent heart failure visit), or cardiovascular death.

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

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.