WILMINGTON, Del.--(BUSINESS WIRE)--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); to improve glycemic control in pediatric patients (10 to 17 years) as an 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 glycemic control compared to placebo in pediatrics.
This is the first completed trial of a once-weekly GLP-1 RA in a pediatric 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.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D said: “This 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 was 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.
The International Coordinating Investigator of the trial, William Tamborlane, MD, Department of Pediatrics, Yale School of Medicine, said: “The 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 glycemic control. It was also approved for use in the EU in August 2018.
BCB114 was a 24-week, randomized, double-blind, placebo-controlled Phase III trial with a 28-week open-label extension. Pediatric 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 randomized to receive exenatide extended-release 2 mg or placebo. The primary efficacy endpoint of the Phase III trial was change in glycated hemoglobin 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).
Overall, the adverse reactions observed in this pediatric population were consistent with that observed in the adult population. Safety and effectiveness of exenatide extended-release have not been established in pediatric patients less than 10 years of age.
INDICATION AND LIMITATIONS OF USE
BYDUREON BCise 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
- Not recommended as first-line therapy for patients inadequately controlled on diet and exercise
- Should not be used to treat type 1 diabetes
- Do not coadminister with other exenatide-containing products
- Not studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF THYROID C-CELL TUMORS
- Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON BCise causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC) in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined
- BYDUREON BCise is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of BYDUREON BCise and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with BYDUREON BCise
- Personal or family history of MTC, patients with MEN 2
- Prior serious hypersensitivity reactions to exenatide or product components
- History of drug-induced, immune-mediated thrombocytopenia from exenatide products
WARNINGS AND PRECAUTIONS
- Acute Pancreatitis including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been reported. After initiation, observe patients carefully for symptoms of pancreatitis. If suspected, discontinue promptly and do not restart if confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis
- Hypoglycemia Risk of hypoglycemia, including severe hypoglycemia, is increased when exenatide is coadministered with insulin or insulin secretagogues. Consider lowering the dose of these agents when coadministered with BYDUREON BCise
- Acute Kidney Injury May induce nausea and vomiting with transient hypovolemia and may worsen renal function. Increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation have been reported. Not recommended in patients with eGFR <45 mL/min/1.73 m
- Gastrointestinal Disease Because exenatide is commonly associated with gastrointestinal adverse reactions, not recommended in patients with severe gastrointestinal disease (eg, gastroparesis)
- Immunogenicity Patients may develop antibodies to exenatide. Patients with higher titer antibodies may have an attenuated HbA1c response. In clinical trials, attenuated glycemic response was associated with BYDUREON BCise-treated patients. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy
- Hypersensitivity Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON BCise and promptly seek medical advice
- Drug-induced, immune-mediated thrombocytopenia and associated bleeding has been reported with exenatide. Serious bleeding, which may be fatal, has been reported. Discontinue promptly if suspected and avoid re-exposure to exenatide
- Injection-Site Reactions Serious reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, have been reported
- Acute Gallbladder Disease has been reported in GLP-1 receptor agonist trials, including exenatide. If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated
Most common (≥5%) in clinical trials: injection-site nodule (10.5%), nausea (8.2%). Adverse reactions in patients 10 to 17 years of age treated with BYDUREON (exenatide extended-release) were similar to that in adults
- Oral Medications BYDUREON BCise slows gastric emptying and may reduce the rate of absorption of orally administered drugs
- Warfarin Increased international normalized ratio (INR) sometimes associated with bleeding has been reported with concomitant use of exenatide with warfarin. Monitor INR frequently until stable upon initiation of BYDUREON BCise
Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Type 2 Diabetes
T2D is a chronic disease characterized by pathophysiologic defects leading to elevated glucose levels, or hyperglycemia. Over time, this sustained hyperglycemia contributes to further progression of the disease. The prevalence of diabetes is projected to reach 578 million people worldwide by 2030, and 700 million by 2045 T2D accounts for approximately 90–95 percent of all cases of diagnosed diabetes.
The incidence of T2D in children and adolescents is increasing worldwide possibly due to the obesity epidemic.
BCB114 Phase III trial
BCB114 was a Phase III, double-blind, placebo-controlled, randomized, multi-center, 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 glycemic control compared to placebo in pediatrics. It is the first completed trial of a once-weekly GLP-1 RA in pediatrics 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 glycemic control in adults with T2D, the BCB114 trial was designed to evaluate the effects of exenatide extended-release on glycemic control in pediatrics with T2D.
AstraZeneca in CV, Renal & Metabolism (CVMD)
CV (cardiovascular), renal, and metabolism (CVMD) together form one of AstraZeneca’s main therapy areas, which has become 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 improving outcomes by slowing disease progression, reducing risks, and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVMD 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization 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. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.