Forxiga met primary endpoint in T2NOW Phase III trial, one of the largest paediatric type 2 diabetes studies performed to date
PUBLISHED4 October 2023
Clinically meaningful improvements in glycaemic control among patients aged 10-17 years compared to placebo
Prevalence of type 2 diabetes in children continues to increase, yet limited oral treatment options are available
Positive results from the T2NOW Phase III trial demonstrated significant reduction in A1C, a marker of average blood sugar, for patients treated with Forxiga (dapagliflozin) compared with patients receiving placebo.1,2 Adjusted mean change in A1C was −0.62% for Forxiga versus +0.41% for placebo, a difference of −1.03% (95% CI: -1.57-0.49; p<0.001). Statistical significance was achieved in the primary endpoint and in all secondary endpoints versus placebo at week 26, establishing that Forxiga can provide clinically meaningful improvements in glycemia for children and adolescents with type 2 diabetes (T2D).1 The safety results in this patient population were consistent with those in adults with T2D, in line with the well-established safety profile for Forxiga.1
Naim Shehadeh, Professor of Endocrinology, Rambam Health Care Campus, Israel, said: “The significant decrease in A1C that we observed in patients receiving Forxiga may indicate a reduction in the progression of disease and its complications. This is an important treatment consideration as children and adolescents with type 2 diabetes often experience earlier onset of complications and faster advancement of disease compared to adults with the same condition.”
Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Today’s results from one of the largest studies into children suffering from type 2 diabetes, offers hope. Despite the growing global burden of type 2 diabetes among children and adolescents, the treatment options available are currently limited. It is well documented that some patients find injectable therapies challenging, making the need for effective oral treatment alternatives paramount.”
Results were presented today at the 59th Annual Meeting of the European Association for the Study of Diabetes (EASD) Congress and simultaneously published in The New England Journal of Medicine Evidence.1
The incidence and prevalence of T2D in children and adolescents are increasing globally.3 In 2021, it was estimated that there were approximately 41,600 new cases diagnosed worldwide.3
Notes
T2D
T2D is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycaemia.4 Over time, this sustained hyperglycaemia contributes to further progression of the disease.4 The prevalence of diabetes is projected to reach 783 million by 2045.4 T2D is the most common type of diabetes, accounting for over 90% of all diabetes worldwide.5 Significant unmet medical need still exists, as many patients have poor blood sugar control and low medication adherence.4,6
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.7 Patients were randomised to dapagliflozin, saxagliptin or placebo.7 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.7 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).7 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.7
Forxiga
Forxiga (dapagliflozin) is a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor. 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.8-10 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).11-14
As of August 2023, Forxiga was approved in 122 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 study.15,16 Forxiga is currently not approved for use in paediatric patients with T2D in the US.
In addition, Forxiga is approved for the treatment of heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in more than 100 countries around the world. It has most recently received regulatory approvals across major geographies to extend the heart failure indication to include patients across the full left ventricular ejection fraction range.
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 (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 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca
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References
1. Shehadeh N, et al. Dapagliflozin vs Placebo and Saxagliptin vs Placebo in Children and Adolescents with type 2 diabetes: Results from the Phase 3 T2NOW study. New England Journal of Medicine. 2023 Oct; 1-27
2.CDC [Internet]. All About Your A1C (cited 1 September 2023]). Available from: https://www.cdc.gov/diabetes/managing/managing-blood-sugar/a1c.html#:~:text=The%20A1C%20test%E2%80%94also%20known,care%20team%20manage%20your%20diabetes.
3. 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.
4. International Diabetes Federation [Internet]. IDF Diabetes Atlas Tenth Edition 2021. (cited 1 September 2023). Available from: https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf
5. Weng J, et al. Standards of care for type 2 diabetes in China. Diabetes Metab Res Rev. 2016 ;32(5):442-58.
6. Blüher M, et al. Pill Burden in Patients With Type 2 Diabetes in Germany: Subanalysis From the Prospective, Noninterventional PROVIL Study. 2015; 33(2): 55–61.
7. Galassetti P, et al. Dapagliflozin in children and adolescents (age 10-17 years) with type 2 diabetes. Presented at: EASD 2023, 2-6 October 2023, Hamburg, Germany.
8. McMurray JJV, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
9. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.
10. 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.
11. Mayo Clinic [Internet]. Heart failure [last accessed 1 September 2023]. Available from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
12. 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.
13. Centers for Disease Control and Prevention (CDC) [Internet]. A snapshot: Diabetes in the United States; (cited 1 September 2023). Available from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.
14. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet]. Heart disease & kidney disease; (cited 1 September 2023). Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease
15. European Medicines Agency (EMA). Forxiga 5mg/ 10mg film-coated tablets - Summary of product characteristics.(Cited 12 September 2023) Available at: https://www.ema.europa.eu/en/documents/product-information/forxiga-epar-product-information_en.pdf.
16. Clinicaltrials.gov. Study to Evaluate Safety and Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Aged 10-24 Years. (cited 12 September 2023). Available at: https://classic.clinicaltrials.gov/ct2/show/results/NCT02725593
Source:- Astrazeneca
