Updated safety data on risk-benefit profile of Farxiga (dapagliflozin), three new analyses from the landmark CVD-REAL study, including Farxiga vs DPP-4 inhibitors, and a late-breaking oral presentation reveal further CV evidence across a broad population of patients with type-2 diabetes
Data from DURATION-7 and DURATION-8 evaluating efficacy and safety of Bydureon (exenatide extended-release) in combination with basal insulin and Farxiga, respectively
More than 50 abstracts demonstrate commitment to Cardiovascular and Metabolic Diseases
AstraZeneca and its global biologics research and development arm, MedImmune, will present the latest research from the Company’s Cardiovascular and Metabolic Diseases (CVMD) therapy area, including for Farxiga (dapagliflozin) and Bydureon (exenatide extended-release) for injectable suspension, with more than 50 abstracts at the American Diabetes Association’s (ADA) 77th Scientific Sessions in San Diego, USA 9-13 June 2017.
Ludovic Helfgott, Vice President, CVMD, said: “Science points to the need to move beyond lowering blood sugar to treat patients with type-2 diabetes holistically and earlier in their disease progression. Through investment in rigorous clinical and real-world evidence studies in large and diverse patient populations, we are committed to advancing scientific understanding of the connections between these highly-prevalent cardiovascular and metabolic diseases and helping to enhance clinical practice to improve the lives of patients.”
Highlights include a comprehensive updated safety analysis of dapagliflozin and three additional analyses from the landmark CVD-REAL real-world evidence study, including CV data for dapagliflozin, evaluating the risk of hospitalization for kidney disease and heart failure (HF), as well as all-cause mortality, compared to DPP-4 inhibitors, a commonly-used treatment for type-2 diabetes (T2D). Additionally, a late-breaking oral presentation will explore the rates of HF and death in patients with T2D, both with and without cardiovascular disease, receiving treatment with SGLT-2 inhibitors (SGLT-2i) versus other T2D medicines.
Also presented will be the baseline characteristics and trial design of DECLARE will be presented, the largest cardiovascular outcomes trial in the SGLT-2i class. Both CVD-REAL and DECLARE are part of the extensive DapaCare programme for dapagliflozin, which involves patients with and without T2D to generate data across established CV disease, CV risk factors and varying stages of renal disease, providing healthcare providers with evidence needed to improve patient care.
AstraZeneca will also present analyses from DURATION-8, evaluating the investigational use of exenatide extended-release in combination with dapagliflozin, as well as primary data from DURATION-7, examining the investigational use of exenatide extended-release in combination with basal insulin.
Notable data being presented by AstraZeneca include:
Real-World Evidence Evaluating CV Outcomes Treatment with SGLT-2 inhibitors
- Evaluation of SGLT2i on Risk of Mortality and Heart Failure Compared to Other Glucose Lowering Drugs: A Three-country Analysis (Poster 1205-P, Sunday June 11, 12:00 p.m. PDT)
- Hospitalization for Heart Failure and Death in New Users of SGLT2 Inhibitors in patients With and Without Cardiovascular Disease – CVD-REAL Study (Oral 377-OR, Tuesday June 13, 10:45 a.m. PDT)
- Evaluation of dapagliflozin on Risk of Hospitalization for Kidney Disease, Heart Failure and All-Cause Death Compared to DPP-4i: CVD-REAL Nordic (Late-Breaker 165-LB, Sunday June 11, 12:00 p.m. PDT)
Comprehensive New Safety Analysis of Dapagliflozin
- Safety Update on dapagliflozin (DAPA) Across the Phase 2b/3 Clinical Trial Program (Poster 1263-P, Sunday June 11, 12:00 p.m. PDT)
DECLARE Trial Design and Baseline Characteristics
- DECLARE-TIMI 58: Design and Baseline Characteristics (Poster 1245-P, Sunday June 11, 12:00 p.m. PDT)
Data Assessing GLP-1 Receptor Agonists with Other Antidiabetic Agents
- Efficacy and Safety of exenatide QW Versus Placebo Added to Insulin Glargine in Uncontrolled Basal-Insulin Treated type-2 Diabetes: DURATION-7 Trial (Oral 132-OR, Saturday June 10, 4:45 p.m. PDT)
- DURATION-8 Randomized Controlled Trial 1-Year Results: Efficacy and Safety of Once-Weekly Exenatide (ExQW) Plus Once-Daily Dapagliflozin (DAPA) Versus ExQW or DAPA Alone (Late-Breaker Poster 141-LB, Sunday June 11, 12:00 p.m. PDT)
- Effects of exenatide Once Weekly Plus dapagliflozin, exenatide Once Weekly, or dapagliflozin Added to metformin Monotherapy on Cardiovascular Risk Markers in Patients with type-2 diabetes in the DURATION-8 trial (Poster 1152-P, Sunday June 11, 12:00 p.m. PDT)
- DURATION-8: Mechanisms of Glycemic Control for exenatide Plus dapagliflozin Versus Each Drug Alone (Poster 1074-P, Sunday June 11, 12:00 p.m. PDT)
- Exenatide Once Weekly (QW) Plus dapagliflozin, exenatide QW, or dapagliflozin Added to metformin Monotherapy in Subgroups of Patients with type-2 Diabetes in the DURATION-8 Study (Poster 1115-P, Sunday June 11, 12:00 p.m. PDT)
The full list of AstraZeneca scientific presentations can be accessed on the ADA website here.
Indication and Limitations of Use for FARXIGA® (dapagliflozin)
FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Important Safety Information for FARXIGA® (dapagliflozin)
- Prior serious hypersensitivity reaction to FARXIGA
- Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
Warnings and Precautions
- Hypotension: FARXIGA causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating FARXIGA in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension
- Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
- Acute Kidney Injury and Impairment in Renal Function: FARXIGA causes intravascular volume contraction and renal impairment, with reports of acute kidney injury requiring hospitalization and dialysis. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat.
FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating FARXIGA, evaluate renal function and monitor periodically. FARXIGA is not recommended in patients with an eGFR persistently between 30 and <60 mL/min/1.73 m2
- Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections [UTIs] and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
- Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
- Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
- Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur with FARXIGA. Monitor LDL-C and treat per standard of care
- Bladder cancer: An imbalance in bladder cancers was observed in clinical trials. There were too few cases to determine whether the emergence of these events is related to FARXIGA, and insufficient data to determine whether FARXIGA has an effect on preexisting bladder tumors. FARXIGA should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
- Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with FARXIGA
In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).
Use in Specific Populations
- Pregnant Women: There are no adequate and well-controlled studies of FARXIGA in pregnant women. Consider appropriate alternative therapies, especially during the second and third trimesters. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus
- Nursing Mothers: Discontinue FARXIGA or discontinue nursing
Indication And Limitations Of Use for BYDUREON® (exenatide extended-release) for injectable suspension
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
Important Safety Information for BYDUREON® (exenatide extended-release) for injectable suspension
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
NOTES TO EDITORS
About the DapaCare Clinical Program
AstraZeneca is taking a holistic, patient-centric approach to disease management by focusing on the underlying morbidity, mortality and organ damage associated with cardiovascular (CV), metabolic and renal diseases. Due to the interconnectivity of these diseases, AstraZeneca has developed the DapaCare clinical programme to explore the CV and renal profile of dapagliflozin in people with and without type-2 diabetes. The clinical programme will enroll nearly 30,000 patients in randomized clinical trials and is supported by a multinational real-world evidence study. DapaCare will generate data across a spectrum of people with established CV disease, CV risk factors and varying stages of renal disease, both with and without type-2 diabetes, providing healthcare providers with evidence needed to potentially improve patient outcomes. DapaCare underscores our commitment to following the science by pursuing a holistic patient approach to address the multiple risk factors associated with CV, metabolic and renal diseases. Dapagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Dapagliflozin is not indicated for the treatment of other metabolic diseases, to reduce the risk of cardiovascular disease or renal 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.
Michele Meixell +1 302 885 2677
Alex Engel +1 302 885 2677
10527 Last Updated 5/17