FARXIGA met primary endpoint in DELIVER Phase III trial, reducing risk of cardiovascular death or worsening heart failure in patients with preserved ejection fraction
Results from the DELIVER and DAPA-HF Phase III trials demonstrate FARXIGA’s efficacy in heart failure regardless of ejection fraction
HF is a chronic, long-term condition that worsens over time1. It affects nearly 64 million people globally2 and is associated with substantial morbidity and mortality3. There are several main categories of HF related to ejection fraction (EF), a measurement of the percentage of blood leaving the heart each time it contracts including: HF with reduced EF (HFrEF) (LVEF less than or equal to 40%), HF with mildly reduced EF (HFmrEF) (LVEF 41-49%) and preserved EF (HFpEF) (LVEF greater than or equal to 50%)4. Approximately half of all HF patients have mildly reduced or preserved EF with few therapeutic options available4,5. FARXIGA already has approved indications relating to the treatment of type 2 diabetes (T2D), HFrEF and chronic kidney disease (CKD).
The safety and tolerability profile of FARXIGAin the DELIVER Phase III trial were consistent with the well-established safety profile of the medicine.
The full DELIVER Phase III trial results will be submitted for presentation at a forthcoming medical meeting and regulatory submissions will be made in the coming months.
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 diseaseat 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.
To improve glycemic control, the recommended starting dose is 5 mg orally once daily. Dose can be increased to 10 mg orally once daily for additional glycemic control.
For all other indications, the recommended dose is 10 mg orally once daily.
IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5 mg and 10 mg tablets
- Prior serious hypersensitivity reaction to FARXIGA
- Patients on dialysis
Warnings and Precautions
- Ketoacidosis in Diabetes Mellitushas 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, 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
- 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
- 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
Please see link to US Full Prescribing Information for FARXIGA.
HF affects approximately 64 million people worldwide2, at least half of whom have a reduced EF6, including approximately 15 million in the
DELIVER was an international, randomized, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of FARXIGA, compared with placebo, in the treatment of HF patients with LVEF greater than 40% with or without T2D. FARXIGA was given once daily in addition to background therapy (regional standard of care for all comorbidities, including diabetes and hypertension, with the exception of concomitant use of a sodium-glucose cotransporter 2 [SGLT2] inhibitor)13.DELIVER is the largest clinical trial to date in HF patients with EF above 40%, with 6,263 randomized patients13, 14.
The primary endpoint was the time to first occurrence of CV death, hospitalization for HF (hHF) or an urgent HF visit. The secondary endpoint includes the total number of HF events (hHF or urgent HF visit) and CV death, change from baseline in the total symptom score of the Kansas City Cardiomyopathy Questionnaire at eight months, time to the occurrence of CV death and time to the occurrence of death from any cause13.
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas,
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