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
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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- Shehadeh N, et al. Dapagliflozin or Saxagliptin in Pediatric
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- Pavkov ME, et al. Effect of youth-onset type 2 diabetes
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- Copeland KC, et al. Characteristics of adolescents and youth
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- Constantino MI, et al. Long-term complications and mortality in
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than type 1 diabetes. Diabetes Care. 2013;36:3863-9.
- Jaiswal M, et al. Prevalence of and Risk Factors for Diabetic
Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes:
SEARCH for Diabetes in Youth Study. Diabetes Care.
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- Kim JY, et al. Adipose Tissue Insulin Resistance in Youth on
the Spectrum From Normal Weight to Obese and From Normal Glucose
Tolerance to Impaired Glucose Tolerance to Type 2 Diabetes.
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- Utzschneider K, et al. Differential loss of β-cell function in
youth vs. adults following treatment withdrawal in the Restoring
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- Barrett T, et al. Novo Nordisk Pediatric Type 2 Diabetes Global
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- Centers for Disease Control and Prevention (CDC) [Internet].
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https://www.cdc.gov/diabetes/diabetes-testing/prediabetes-a1c-test.html.
[Last accessed: 6 June 2024].
- European Medicines Agency (EMA) [Internet]. Forxiga 5mg/ 10mg
film-coated tablets - Summary of product characteristics. Available
at:
https://www.ema.europa.eu/en/documents/product-information/forxiga-epar-product-information_en.pdf.
[Last accessed: 6 June 2024].
- Clinicaltrials.gov [Internet]. Study to Evaluate Safety and
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Aged 10-24 Years. Available at:
https://classic.clinicaltrials.gov/ct2/show/results/NCT02725593.
[Last accessed: 6 June 2024].
- Weng J, et al. Standards of care for type 2 diabetes in China.
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- Blüher M, et al. Pill Burden in Patients With Type 2 Diabetes
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- Jhund P, et al. Dapagliflozin across the range of ejection
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- Heerspink HJL, et al. Dapagliflozin in patients with chronic
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- Wiviott SD, et al. for the DECLARE-TIMI 58 Investigators.
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