BYDUREON EXSCEL Trial Meets Primary Safety Objective in Type-2 Diabetes Patients at Wide Range of Cardiovascular Risk
May 23 2017 - 7:05AM
Business Wire
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 Bj�rk, 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
CONTRAINDICATIONS
- 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
ADVERSE REACTIONS
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%)
DRUG INTERACTIONS
- 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
Please click here for Full Prescribing Information
and click here for Medication Guide for BYDUREON 2 mg,
including Boxed WARNING.
NOTES TO EDITORS
About EXSCEL
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.
About AstraZeneca
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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170523005667/en/
AstraZenecaMedia:Michele Meixell +1
302-885-2677orAlex Engel +1 302-885-2677
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Apr 2024 to May 2024
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From May 2023 to May 2024