AstraZeneca's Farxiga (dapagliflozin) has been approved by the US Food and Drug Administration (FDA) to improve glycaemic control in paediatric patients with type-2 diabetes (T2D) aged 10 years and older.[1] The FDA approval was based on positive results from the paediatric 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 glycaemic 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 paediatric 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 (https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300210), 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 glycaemia 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. Forxiga is also approved for paediatric 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.

Notes

T2D
T2D is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycaemia.[3 ]Over time, this sustained hyperglycaemia 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 randomised, 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 randomised to dapagliflozin, saxagliptin or placebo.[2] Those receiving an active drug were further randomised 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
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, Forxiga was approved in 126 countries as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Forxiga is approved for paediatric patients aged 10 years and above with T2D in the EU and other countries based on the T2GO trial.[17,18]

In addition, Forxiga 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. Forxiga was the first heart failure medication to demonstrate mortality benefit across the full ejection fraction range.[21]

Research has shown Forxiga'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 (https://www.astrazeneca.com/our-therapy-areas/cardiovascular-renal-and-metabolism.html)
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 (https://www.astrazeneca.com/)
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the Company on social media @AstraZeneca (https://gateway.zscalertwo.net/auD?origurl=https:%2f%2fwww.linkedin.com%2fcompany%2fastrazeneca&_ordtok=Mkk3WV5DBDPmQrD4F5MGdGDMZR)

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References

1. Farxiga (dapagliflozin) US prescribing information; 2024.
2. Shehadeh N, et al. Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes. N Engl J Med Evid. 2023;2(12):1-27.
3. International Diabetes Federation [Internet]. IDF Diabetes Atlas Tenth Edition 2021. Available from: https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf. [Last accessed: 6 June 2024].
4. National Insitute of Diabetes and Digestive and Kidney Diseases (NIDDKD) [Internet]. Type 2 Diabetes. Available at: https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/type-2-diabetes#:~:text=You%20can%20develop%20type%202%20diabetes%20at%20any,of%20diabetes%2C%20or%20are%20overweight%20or%20have%20obesity (https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/type-2-diabetes#:~:text=You%20can%20develop%20type%202%20diabetes%20at%20any,of%20diabetes%2C%20or%20are%20overweight%20or%20have%20obesity.). [Last accessed: 6 June 2024].
5. Wu H, et al. Worldwide estimates of incidence of type 2 diabetes in children and adolescents in 2021. Diabetes Res Clin Pract. 2022;185:109785.
6. Tönnies, T., et al. Projections of Type 1 and Type 2 Diabetes Burden in the U.S. Population Aged <20 Years Through 2060: The SEARCH for Diabetes in Youth Study. Diabetes Care. 2023;46(2):313-320.
7. Centers for Disease Control and Prevention (CDC) [Internet]. Diabetes - National Diabetes Statistics Report. Available at: https://www.cdc.gov/diabetes/php/data-research/index.html (https://www.cdc.gov/diabetes/php/data-research/index.html.). [Last accessed: 6 June 2024].
8. Hillier TA, et al. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care. 2003;26:2999-3005.
9. Pavkov ME, et al. Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. JAMA. 2006;296:421-6.
10. Copeland KC, et al. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96:159-67.
11. Constantino MI, et al. Long-term complications and mortality in young-onset diabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes. Diabetes Care. 2013;36:3863-9.
12. 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. 2017;40:1226-32.
13. 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. Diabetes Care. 2019;42:265-72.
14. Utzschneider K, et al. Differential loss of β-cell function in youth vs. adults following treatment withdrawal in the Restoring Insulin Secretion (RISE) study. Diabetes Res Clin Pract. 2021;178:108948.
15. Barrett T, et al. Novo Nordisk Pediatric Type 2 Diabetes Global Expert P. Rapid progression of type 2 diabetes and related complications in children and young people-A literature review. Pediatric diabetes. 2020;21:158-72.
16. Centers for Disease Control and Prevention (CDC) [Internet]. Testing for Diabetes and Prediabetes: A1C. Available from: https://www.cdc.gov/diabetes/diabetes-testing/prediabetes-a1c-test.html. [Last accessed: 6 June 2024].
17. 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].
18. Clinicaltrials.gov [Internet]. Study to Evaluate Safety and Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Aged 10-24 Years. Available at: https://classic.clinicaltrials.gov/ct2/show/results/NCT02725593. [Last accessed: 6 June 2024].
19. Weng J, et al. Standards of care for type 2 diabetes in China. Diabetes Metab Res Rev. 2016 ;32(5):442-58.
20. Blüher M, et al. Pill Burden in Patients With Type 2 Diabetes in Germany: Subanalysis From the Prospective, Noninterventional PROVIL Study. Clin Diabetes. 2015;33(2):55-61.
21. Jhund P, et al. Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER. Nat Med. 2022; 28(9):1956-1964.
22. McMurray JJV, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
23. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.
24. Wiviott SD, et al. for the DECLARE-TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [article and supplementary appendix]. N Engl J Med. 2019;380(4):347-357.
25. Mayo Clinic [Internet]. Heart failure. Available from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142. [Last accessed: 6 June 2024].
26. Vos T, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211-1259.
27. Centers for Disease Control and Prevention (CDC) [Internet]. A Report Card: Diabetes in the United States. Available from: A Report Card: Diabetes in the United States | Diabetes | CDC (https://www.cdc.gov/diabetes/communication-resources/diabetes-statistics.html). [Last accessed: 6 June 2024]
28. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet]. Heart disease & kidney disease. Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease. [Last accessed: 6 June 2024].