• FDA approval means patients with heart failure can benefit from FARXIGA regardless of left ventricular ejection fraction status

WILMINGTON, Del. / May 09, 2023 / Business Wire / AstraZeneca’s FARXIGA (dapagliflozin) has been approved in the US to reduce the risk of cardiovascular (CV) death, hospitalization for heart failure (hHF) and urgent heart failure (HF) visits in adults with HF. The approval by the Food and Drug Administration (FDA) was based on positive results from the DELIVER Phase III trial.¹ FARXIGA was previously approved in the US for adults with HF with reduced ejection fraction (HFrEF).

Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Approximately half of heart failure patients die within five years of diagnosis, highlighting an urgent unmet need for well-tolerated treatment options that can bring life-saving benefits and reduce the risk of cardiovascular death. The approval of FARXIGA in the US not only reinforces AstraZeneca’s commitment to reducing the burden of this complex and life-threatening disease, but will help patients across the full spectrum of heart failure lead healthier lives.”

HF is a chronic, long-term condition that worsens over time² and affects almost seven million people in the US.³ It is also the leading cause of hospitalization for those over 65 years and represents a significant clinical and economic burden.⁴ Approximately half of all HF patients have HF with mildly reduced ejection fraction (HFmrEF) or HF with preserved ejection fraction (HFpEF)⁵ and these patients are not only at greater risk of death and hospitalizations but experience an especially high burden of symptoms and physical limitations, and a poor quality of life.⁶

The data from the DELIVER Phase III trial, published in The New England Journal of Medicine, showed FARXIGA reached a statistically significant and clinically meaningful early reduction in the primary composite endpoint of CV death or worsening HF in patients with HF with HFmrEF or HFpEF.¹ The results from a pre-specified, pooled analysis of the DAPA-HF and DELIVER Phase III trials, published in Nature Medicine, showed that the treatment effect of FARXIGA on the composite endpoint of cardiovascular death, hospitalization for heart failure or urgent heart failure was consistent across the left ventricular ejection fraction (LVEF) range and established FARXIGA as the first sodium-glucose cotransporter 2 (SGLT2) inhibitor to demonstrate a mortality benefit.⁷

FARXIGA is approved for the treatment of patients with type 2 diabetes (T2D), HFrEF and chronic kidney disease (CKD) in more than 100 countries around the world including the US, the European Union (EU), China and Japan. It has most recently received regulatory approvals in the EU, Great Britain, Japan and Turkey to extend the HF indication to include patients across the full LVEF range.

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, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure
• 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.

DOSING

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

Contraindications

Prior serious hypersensitivity reaction to FARXIGA

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, 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

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

Please see link to US Full Prescribing Information for FARXIGA.

Notes

HF

HF is a chronic, long-term condition that worsens over time.² It affects nearly 64 million people globally⁸ and is associated with substantial morbidity and mortality.⁹ Chronic HF is the leading cause of hospitalization for those over the age of 65 and represents a significant clinical and economic burden.⁴ There are several types of HF often defined by LVEF, a measurement of the percentage of blood leaving the heart each time it contracts, including: HFrEF (LVEF less than or equal to 40%), HFmrEF (LVEF 41-49%) and HFpEF (LVEF greater than or equal to 50%).¹⁰ Approximately half of all HF patients have HFmrEF or HFpEF,⁵ with few therapeutic options available.⁶

DELIVER

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 SoC for all comorbidities, including diabetes and hypertension, with the exception of concomitant use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor). DELIVER is the largest clinical trial to date in HF patients with LVEF above 40%, with 6,263 randomized patients.¹¹

The primary composite endpoint was the time to first occurrence of CV death, hHF or an urgent HF visit. Key secondary endpoints include the total number of HF events (hHF or urgent HF visit) and CV death, change from baseline in the total symptom score of the KCCQ at eight months, time to the occurrence of CV death and time to the occurrence of death from any cause.¹¹

AstraZeneca in CVRM

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, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM 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 in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

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References

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