AstraZeneca PLC Release: Astrazeneca Presents New Data Underpinning Safety Profile And Real-World CV Outcomes Of Farxiga At American Diabetes Association 2017

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca presented new data at the American Diabetes Association’s (ADA) 77th Scientific Sessions underpinning the safety profile of Farxiga (dapagliflozin) with an analysis of data pooled from dapagliflozin clinical trials, as well as three new cardiovascular (CV) outcomes analyses from the ongoing CVD-REAL study, the first large real-world evidence study of its kind evaluating treatment with SGLT-2 inhibitors (SGLT-2i), including dapagliflozin.

In an updated safety analysis, data pooled from 30 Phase IIb/III clinical trials for dapagliflozin showed no new safety signals and the incidence of adverse events was generally similar to that in the control groups. Importantly, there was no imbalance in lower-limb amputations, with eight (0.1%) patients and seven (0.2%) patients identified in the dapagliflozin and control groups, respectively.

Following the primary publication of the CVD-REAL study in May 2017, three new analyses presented at ADA add to the ongoing evaluation of earlier treatment with SGLT-2is and in broader patient populations with type-2 diabetes (T2D). The analyses evaluated effects in additional real-world patient populations, including CV endpoints specific to dapagliflozin:

• A two-country analysis of more than 30,000 patients with T2D showed a significant reduction in the rates of hospitalization for kidney disease by 62% (p<0.001), hospitalization for heart failure (HF) by 37% (p<0.001) and death from any cause by 27% (p=0.003) for patients using dapagliflozin versus DPP-4 inhibitors (DPP-4is)
• A three-country analysis of nearly 100,000 patients with T2D showed a significant reduction in rates of CV death by 47% (p<0.001) and hospitalization for HF by 30% (p<0.001), for patients new to SGLT-2is versus other T2D medicines
• A late-breaking oral presentation analyzing data from more than 300,000 patients across five countries will explore the rates of HF and death in patients with T2D, both with and without CV disease, receiving treatment with SGLT-2is versus other T2D medicines (Oral 377-OR, Tuesday June 13, 10:45am PDT)

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, said: “SGLT-2 inhibitors are being prescribed with greater frequency for patients with type-2 diabetes, so it is vital that we have a clear understanding of the safety profile of these medicines and examine their effectiveness in a real-world setting. The data we are presenting at ADA underpins the safety of Farxiga and highlights the potential for earlier use of the SGLT-2 inhibitor class, and in broader patient populations than originally understood.”

The CVD-REAL study is ongoing and future analyses will be conducted using this dataset as well as data from additional countries. The data for the study were obtained from anonymized real-world sources including medical records, claims databases and national registries, and were not independently adjudicated or verified against source documents. The analysis was validated by the independent academic statistical group at St. Luke’s Mid America Heart Institute, Kansas City, USA. While CVD-REAL was a large study with a robust propensity-matching technique, given its observational nature the possibility of residual, unmeasured confounding factors cannot be definitively excluded.

Farxiga is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D. Farxiga is not indicated to reduce the risk of CV events, death or hospitalization for heart failure. The dapagliflozin cardiovascular outcomes trial, DECLARE, is ongoing and expected to provide data in 2019 at the latest.

Important Safety Information for FARXIGA^® (dapagliflozin)

Contraindications

• 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

Adverse Reactions

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 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.

Please see accompanying US Full Prescribing Information and Medication Guide for FARXIGA.

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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.

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.