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Bydureon BCise (exenatide extended-release) is the first once-weekly GLP-1 RA treatment option for paediatric patients with type-2 diabetes mellitus in the US
AstraZeneca’s Bydureon BCise (exenatide extended-release), once-weekly injectable suspension has been approved in the US for the treatment of type-2 diabetes (T2D) mellitus; to improve glycaemic control in paediatric patients (10 to 17 years) adjunct to diet and exercise.
The approval by the US Food and Drug Administration (FDA) is the first regulatory approval for a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) in this population, supported by the positive results of the BCB114 Phase III trial in youth with T2D between 10 and <18 years of age; which showed on top of standard of care exenatide extended-release significantly improved glycaemic control compared to placebo in paediatrics.1
This is the first completed trial of a once-weekly GLP-1 agonist in a paediatric population with T2D. The approval is an important development in diabetes care for this specific group of patients as the only non-insulin options for adolescents are metformin and liraglutide.2,3
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D said: “Today’s decision is an important milestone for the care of this younger patient population by providing a convenient, once-weekly treatment option. The Phase III data that supported this approval demonstrated the safety and tolerability of exenatide extended-release in younger patients similar to the proven safety profile of this medicine in adults.”
Nearly four decades ago, T2D in children was considered rare, but the global rate has been increasing since the mid-1990s, particularly in the US, as the percentage of children who are overweight or obese has risen.4,5,10
The International Coordinating Investigator of the trial, William Tamborlane, MD, Department of Paediatrics, Yale School of Medicine, said: “Today’s US FDA approval is an important milestone for the treatment of children with type-2 diabetes. Bydureon BCise brings an important new therapeutic option to physicians caring for children with this chronic disease that can lead to serious long-term issues if not adequately treated.”
Bydureon BCise (exenatide extended-release) was first approved in the US in October 2017 as a once-weekly single-dose autoinjector device for adults with T2D whose blood sugar remains uncontrolled on one or more oral medicines in addition to diet and exercise, to improve glycaemic control. It was also approved for use in the EU in August 2018.6,7
BCB114 was a 24-week, randomised, double-blind, placebo-controlled Phase III trial with a 28-week open-label extension. Paediatric patients aged 10 to 17 years (N=82) with T2D treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin were randomised to receive exenatide extended-release 2 mg or placebo. The primary efficacy endpoint of the Phase III trial was change in glycated haemoglobin A1c (HbA1c) from baseline to week 24. Results demonstrated that patients administered exenatide extended-release achieved a significantly greater mean change in HbA1c from baseline compared to placebo (-0.25%, n=58, baseline A1C 8.13% vs +0.45%, n=24, baseline A1C 8.28%, respectively; p<0.05).1, 15
Overall, the adverse reactions observed in this paediatric population were consistent with that observed in the adult population.1 Safety and effectiveness of exenatide extended-release have not been established in paediatric patients less than 10 years of age.
Type-2 diabetes
T2D is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycaemia. Over time, this sustained hyperglycaemia contributes to further progression of the disease.8 The prevalence of diabetes is projected to reach 578 million people worldwide by 2030, and 700 million by 2045.5 T2D accounts for approximately 90–95 percent of all cases of diagnosed diabetes.9
The incidence of T2D in children and adolescents is increasing worldwide possibly due to the obesity epidemic.10
BCB114 Phase III trial
BCB114 was a Phase III, double-blind, placebo-controlled, randomised, multi-centre, parallel trial assessing the safety and efficacy of exenatide extended-release compared to placebo in youth with T2D between 10 and <18 years of age; which showed on top of standard of care exenatide extended-release significantly improved glycaemic control compared to placebo in paediatrics.1 It is the first completed trial of a once-weekly GLP-1 RA in paediatrics with T2D. The trial included 82 children or adolescents treated with diet and exercise alone or in combination with an oral antidiabetic agent (metformin and/or sulfonylurea [SU]) and/or insulin. As clinical studies have demonstrated that once-weekly exenatide extended-release improved glycaemic control in adults with T2D,11-14 the BCB114 trial was designed to evaluate the effects of exenatide extended-release on glycaemic control in paediatrics with T2D.1
Bydureon BCise
Bydureon BCise (exenatide extended-release) is an injectable prescription medicine that may improve blood sugar (glucose) in adults with T2D mellitus, and should be used along with diet and exercise. Bydureon BCise is currently available in 39 countries worldwide, including the United States and European Union countries. In June 2011, Bydureon was approved for use in the EU in adults on top of other glucose-lowering treatments when these have not provided adequate control and in August 2012 was approved in the US as the first and only once-weekly treatment for T2D in adults. In October 2017, Bydureon BCise was approved in the US as a once weekly treatment for T2D in adults6.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three 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 improve 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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology 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 Twitter @AstraZeneca.
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References
1. ClinicalTrials.gov. Safety and efficacy study of exenatide once weekly in adolescents with type 2 diabetes. NCT01554618. [Internet]. 2021 [cited 2021 May 25]. Available from: https://clinicaltrials.gov/ct2/show/results/NCT01554618?term=NCT01554618&draw=2&rank=1.
2. VICTOZA® US prescribing information. [Internet]. 2020 [cited 2021 May 25]. Available from: https://www.novo-pi.com/victoza.pdf.
3. Drugs.com. Metformin. [Internet]. 2020 [cited 2021 May 25]. Available from: https://www.drugs.com/metformin.html.
4. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics. 2000;105(3 Pt 1):671-680.
5. International Diabetes Federation. IDF Diabetes Atlas, 9th ed. [Internet]. 2019 [cited 2021 May 25]. Available from: https://diabetesatlas.org/upload/resources/material/20200302_133351_IDFATLAS9e-final-web.pdf.
6. Drugs.com. Development timeline for Bydureon. [Internet]. [cited 2021 May 25]. Available from: https://www.drugs.com/history/bydureon.html.
7. The Pharma Letter. BRIEF – EC approves new easy-to-use, once-weekly Bydureon BCise pen for patient with type-2 diabetes. [Internet]. 2018 [cited 15 July 2021]. Available from: https://www.thepharmaletter.com/in-brief/brief-ec-approves-new-easy-to-use-once-weekly-bydureon-bcise-pen-for-patients-with-type-2-diabetes.
8. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;32(Suppl 1):S62-S67.
9. Centers for Disease Control and Prevention (CDC). Diabetes fast facts. [Internet]. Last reviewed 2020 [cited 2021 May 25]. Available from: https://www.cdc.gov/diabetes/basics/quick-facts.html.
10. Reinehr T. Type 2 diabetes mellitus in children and adolescents. World J Diabetes. 2013;4(6):270-281.
11. Henry RR et al. Efficacy and tolerability of exenatide once weekly over 6 years in patients with type 2 diabetes: an uncontrolled open-label extension of the DURATION-1 study. Diabetes Technol Ther. 2016;18(11):677-686.
12. Wysham CH, Rosenstock J, Vetter ML, Dong F, Ohman P, Iqbal N. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes. Diabetes Obes Metab. 2018;20(1):165-172.
13. Guja C, Frias JP, Somogyi A, Jabbour S, Wang H, Hardy E, et al. Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study. Diabetes Obes Metab. 2018;20(7):1602-1614.
14. Jabbour SA, Frias JP, Hardy E, Ahmed A, Wang H, Ohman P, et al. Safety and efficacy of exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy: 52-week results of the DURATION-8 randomized controlled trial. Diabetes Care. 2018;41(10):2136-2146.
15. U.S. Food and Drug Administration. NDA 209210 S-017 Approval with attachment. Silver Spring: U.S. Food and Drug Administration; 2021 p. 30.
Adrian Kemp
Company Secretary
AstraZeneca PLC
Veeva ID: Z4-35599
Date of prep: July 2021