• US patients aged 10 years and older can now benefit from FARXIGA for type-2 diabetes
• Approval based on results from T2NOW, one of the largest pediatric type-2 diabetes Phase III trials to date

WILMINGTON, Del. / Jun 12, 2024 / Business Wire / AstraZeneca’s FARXIGA^® (dapagliflozin) has been approved by the US Food and Drug Administration (FDA) to improve glycemic control in pediatric patients with type-2 diabetes (T2D) aged 10 years and older.¹ The FDA approval was based on positive results from the pediatric T2NOW Phase III trial.² FARXIGA was previously approved in the US in adults with T2D as an adjunct to diet and exercise to improve glycemic control.¹

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca, said: “The prevalence of type-2 diabetes continues to rise in children and adolescents, yet oral treatment options have remained limited for this population. Today’s approval represents an important milestone for pediatric patients living with type-2 diabetes in the US, extending this medicine’s potential benefits to even more patients facing high unmet needs and reinforcing AstraZeneca’s commitment to delivering innovative treatments across cardiovascular, renal and metabolic diseases.”

T2D is a chronic disease affecting people of all ages.^3,4 The incidence and prevalence of T2D in children and adolescents are increasing globally.⁵ In the US, there are nearly 30,000 patients under 20 living with T2D with 5,300 new cases diagnosed each year, according to the US Centers for Disease Control and Prevention and recent research.^6,7 Younger patients often experience earlier onset of complications and faster advancement of disease compared to adults with the same condition.^8-15

Data from the T2NOW Phase III trial, published in The New England Journal of Medicine Evidence, demonstrated a significant reduction in A1C, a marker of average blood sugar, for patients treated with FARXIGA compared to patients receiving placebo.^2,16 Adjusted mean change in A1C was -0.62% for FARXIGA versus +0.41% for placebo, a difference of -1.03% (95% CI: -1.57-0.49; p<0.001).² Statistical significance was achieved in the primary endpoint and in all secondary endpoints versus placebo at week 26, demonstrating FARXIGA can provide clinically meaningful improvements in glycemia for children and adolescents with T2D.² The safety results in this patient population were consistent with those in adults with T2D, in line with the well-characterised safety profile for FARXIGA.²

FARXIGA, a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor, was approved in 126 countries, including the EU (marketed under the brand name Forxiga), as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. FARXIGA is also approved for pediatric patients aged 10 years and above with T2D in 56 countries, including the EU and other regions, based on results from the T2GO Phase III clinical trial.^17,18

Additional regulatory submissions and rollout plans are under consideration pending further market evaluations.

INDICATIONS AND LIMITATIONS OF USE for FARXIGA^® (dapagliflozin)

FARXIGA is indicated:

• as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older 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, endstage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression

FARXIGA is not recommended for use to improve glycemic control in patients with type-1 diabetes mellitus.

FARXIGA is not recommended for use to improve glycemic control in patients 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 in adults and pediatric patients aged 10 years and older with T2D, 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 other indications in adults, the recommended dose is 10 mg orally once daily.

IMPORTANT SAFETY INFORMATION for FARXIGA^® (dapagliflozin) 5 mg and 10 mg

Contraindications 
History of serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA.

Warnings and Precautions

• Ketoacidosis: FARXIGA significantly increases the risk of diabetic ketoacidosis in patients with type-1 diabetes mellitus. Type-2 diabetes mellitus and pancreatic disorders are also risk factors. There have been postmarketing reports of fatal events of ketoacidosis in patients with type-2 diabetes mellitus using SGLT2 inhibitors, including FARXIGA. Consider ketone monitoring in patients with type-1 diabetes mellitus and in others at risk for ketoacidosis. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose levels. If suspected, discontinue FARXIGA, evaluate and treat promptly. Withhold FARXIGA, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume FARXIGA when the patient is clinically stable and has resumed oral intake
• 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 mellitus 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

Most Common Adverse Reactions (≥5%): Female genital mycotic infections, nasopharyngitis, and urinary tract infections.

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

T2D

T2D is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycemia.³ Over time, this sustained hyperglycemia contributes to further progression of the disease.³ The prevalence of diabetes is projected to reach 783 million by 2045.³ T2D is the most common type of diabetes, accounting for over 90% of all diabetes worldwide.¹⁹ Significant unmet medical need still exists, as many patients have poor blood sugar control and low medication adherence.^3,20

T2NOW

T2NOW was a randomized, double-blind, placebo-controlled Phase III trial designed to evaluate the efficacy and safety of dapagliflozin as add-on treatment in children and adolescents with T2D receiving metformin, insulin or both.² Patients were randomized to dapagliflozin, saxagliptin or placebo.² Those receiving an active drug were further randomized to continue their current dose, or up-titrate to a higher dose of the same active treatment.² The primary endpoint was change in A1C after 26 weeks vs placebo for dapagliflozin (5 or 10 mg) or saxagliptin (2.5 or 5 mg).² Secondary endpoints included change in fasting plasma glucose and proportion of patients (A1C ≥7% at baseline) achieving A1C <7.0% (53 mmol/mol) after 26 weeks.²

FARXIGA (dapagliflozin) in the US and marketed as Forxiga in the rest of world, is a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor. As of June 2024, FARXIGA was approved in 126 countries as an adjunct to diet and exercise to improve glycemic control in adults with T2D. FARXIGA is approved for pediatric patients aged 10 years and above with T2D in the EU and other countries based on the T2GO trial.^17,18

In addition, FARXIGA is approved for the treatment of heart failure across the full ventricular ejection fraction range (HFrEF and HFpEF) and CKD in adult patients in more than 100 countries around the world. FARXIGA was the first heart failure medication to demonstrate mortality benefit across the full ejection fraction range.²¹

Research has shown FARXIGA’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas.^22-24 Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, heart failure (HF) and chronic kidney disease (CKD).^25-28

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, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.

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 www.astrazeneca-us.com and follow us on social media @AstraZeneca.

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