AstraZeneca Presents New Data Underpinning Safety Profile and Real-World CV Outcomes of Farxiga at ADA 2017
June 12 2017 - 7:00AM
Business Wire
Comprehensive updated analysis provides
valuable evidence on the safety profile of Farxiga, including no
imbalance in lower-limb amputations
New analyses from CVD-REAL examine reductions
in CV events for SGLT-2 inhibitors, including Farxiga in patients
with and without CV disease versus DPP-4 inhibitors
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 Bj�rk, 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.
– ENDS –
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.
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