Based on a composite measure of major adverse CV events (MACE), Bydureon did not increase cardiovascular (CV) risk and showed a consistent safety profile
Fewer events were observed in the Bydureon arm, however, the efficacy objective of reduction in CV risk did not reach statistical significance
AstraZeneca today announced top-line results from the Phase IIIb/IV EXSCEL (EXenatide Study of Cardiovascular Event Lowering) trial. The trial compared the effect of once-weekly Bydureon (exenatide extended-release) for injectable suspension versus placebo, when added to usual type-2 diabetes care, on the risk of MACE, a composite endpoint of CV death, non-fatal myocardial infarction or non-fatal stroke, in adults with type-2 diabetes (T2D) at a wide range of CV risk.
The EXSCEL trial met its primary safety objective of non-inferiority for MACE. These results address the US Food and Drug Administration (FDA) requirement that medicines to treat T2D are not associated with an increase in CV risk. Fewer CV events were observed in the Bydureon arm of the trial, however, the efficacy objective of superior reduction in MACE did not reach statistical significance. Data were consistent with the known safety profile of Bydureon.
Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca said: “These top-line results from the EXSCEL trial provide robust evidence of the cardiovascular safety profile of Bydureon across a wide range of patients with type-2 diabetes. Furthermore, the trial design and broad inclusion criteria of EXSCEL offer physicians relevant data applicable to clinical practice.”
The EXSCEL trial is the largest and most inclusive patient population of any CV outcomes trial of the glucagon-like peptide-1 (GLP-1) receptor agonist class conducted to date, having included more than 14,000 patients from 35 countries.
A full evaluation of the EXSCEL data is ongoing. The results will be presented at the European Association for the Study of Diabetes (EASD) annual meeting on Thursday, 14 September 2017 in Lisbon, Portugal.
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 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 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 and inform them of symptoms of thyroid tumors (e.g., 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
- Personal or family history of MTC, patients with MEN 2
- Patients with prior serious hypersensitivity reactions to exenatide or to any of the product components
WARNINGS AND PRECAUTIONS
- Pancreatitis Exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. 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 BYDUREON increased the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with BYDUREON
- Renal Impairment Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation has been reported. Not recommended in patients with severe renal impairment or end-stage renal disease. Use caution in patients with renal transplantation or moderate renal failure
- Severe 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. In 5 registration trials, attenuated glycemic response was associated in 6% of BYDUREON-treated patients with antibody formation. 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 and promptly seek medical advice
- Injection-Site Reactions Serious reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, have been reported
- Macrovascular Outcomes No clinical studies establishing conclusive evidence of macrovascular risk reduction with BYDUREON or any other antidiabetic drug
Most common (≥5%) and occurring more frequently than comparator in clinical trials: nausea (16.9%), diarrhea (12.7%), headache (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus (5.9%), injection-site nodule (5.3%), and dyspepsia (5.1%)
- Oral Medications BYDUREON 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
PREGNANT AND NURSING WOMEN
- Pregnant Women Based on animal data, may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Nursing Women Discontinue BYDUREON or discontinue nursing
INDICATION AND LIMITATIONS OF USE
BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- Not recommended as first-line therapy for patients inadequately controlled on diet and exercise
- Not a substitute for insulin, should not be used in patients with type 1 diabetes or diabetic ketoacidosis
- Not recommended for use with insulin
- BYDUREON and BYETTA® (exenatide) injection contain the same active ingredient, exenatide. Do not coadminister with BYETTA
- Not studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis
NOTES TO EDITORS
EXSCEL is a Phase IIIb/IV, double-blind, placebo-controlled, global CV outcomes trial conducted in 35 countries and enrolled more than 14,000 patients with type-2 diabetes with or without additional CV risk factors or prior CV events. Participants were randomized to receive exenatide once-weekly 2mg or matching placebo by subcutaneous injections. EXSCEL was run jointly by two academic research organizations - the Duke Clinical Research Institute (Durham, NC, US) and the University of Oxford Diabetes Trials Unit (Oxford, UK).
About AstraZeneca in Diabetes
AstraZeneca is pushing the boundaries of science with the goal of developing life-changing medicines that aim to reduce the global burden and complications of diabetes. As a main therapy area for the company, we are focusing our research and development efforts on diverse populations and patients with significant co-morbidities, such as cardiovascular disease, obesity, non-alcoholic steatohepatitis (NASH), and chronic kidney disease.
Our commitment to diabetes is exemplified by the depth and breadth of our global clinical research program This commitment is advancing understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination products to help more patients achieve treatment success earlier in their disease.
About AstraZeneca in Cardiovascular & Metabolic Diseases (CVMD)
Cardiovascular, renal and metabolic diseases are key areas of focus for AstraZeneca as part of the company’s strategy for achieving scientific leadership and returning to growth. By collaborating across therapeutic disciplines within the CVMD therapy area, we are addressing the underlying disorders that drive CVMD risk, with the goal of reducing morbidity, mortality and organ damage through innovative therapies. Recognizing the growing unmet needs and challenges faced by the millions of people worldwide living with these interrelated diseases, we are determined to understand how they interact and impact one another – and how they can be treated together to save more patients’ lives.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. 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.
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10527 Last Updated 5/17