FARXIGA met the primary composite endpoint of a
statistically-significant reduction in hospitalization for heart failure
or CV death in a broad patient population
Results confirmed the well-established safety profile of FARXIGA
WILMINGTON, Del. -- (Business Wire)
AstraZeneca today announced positive results from the Phase III
DECLARE-TIMI 58 cardiovascular (CV) outcomes trial (CVOT) for FARXIGA®
(dapagliflozin), the broadest SGLT-2 inhibitor CVOT conducted to date.
The trial evaluated the CV outcomes of FARXIGA vs. placebo over a period
of up to five years, across 33 countries and in more than 17,000 adults
with type 2 diabetes (T2D) who have multiple CV risk factors or
established CV disease.
In the DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI 58
trial, FARXIGA met its primary safety endpoint of non-inferiority for
major adverse cardiovascular events (MACE). FARXIGA achieved a
statistically-significant reduction in the composite endpoint of
hospitalization for heart failure (hHF) or CV death, one of the two
primary efficacy endpoints. Additionally, fewer MACE events were
observed with FARXIGA for the other primary efficacy endpoint, however,
this did not reach statistical significance. FARXIGA is not indicated to
reduce the risk of CV events or hHF.
Data from DECLARE-TIMI 58 confirmed the well-established safety profile
of FARXIGA.
Elisabeth Björk, Vice President, Head of Cardiovascular, Renal and
Metabolism, Global Medicines Development at AstraZeneca said: “FARXIGAhas achieved a statistically-significant and clinically-important
reduction in hospitalization for heart failure or CV death in a broad
range of patients with type 2 diabetes and cardiovascular risk. The
results from this landmark trial are especially important since heart
failure is an early and frequent complication of diabetes and associated
with hospitalizations that result in a considerable societal and
economic burden.” 1-7
Dr Stephen Wiviott of Brigham and Women’s Hospital and Harvard Medical
School, a senior investigator with the Thrombolysis in Myocardial
Infarction (TIMI) study group and co-principal investigator of the
trial, commented: “The DECLARE-TIMI 58 results offer compelling evidence
that dapagliflozin helps to address an important medical need among a
diverse group of patients with type 2 diabetes by reducing the composite
of hospitalization for heart failure or CV death, with a safety profile
supportive of broad use.”
Detailed trial results will be presented on November 10 at the American
Heart Association Scientific Sessions 2018 in Chicago, IL.
INDICATION AND LIMITATIONS OF USE FOR FARXIGA (dapagliflozin) tablets
5 mg and 10 mg
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
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 pre-existing 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
- Pregnancy: Advise females of potential risk to a fetus
especially during the second and third trimesters.
- Lactation: FARXIGA is not recommended when breastfeeding
Please read US
Full Prescribing Information and Medication
Guide for FARXIGA
Notes to Editors:
About DECLARE-TIMI 58:
DECLARE (Dapagliflozin Effect on
Cardiovascular Events)-TIMI-58 is an AstraZeneca-sponsored, randomized,
double-blinded, placebo-controlled, multicenter trial designed to
evaluate the effect of FARXIGA compared with placebo on CV outcomes in
adults with T2D at risk of CV events, including patients with multiple
CV risk factors or established CV disease. DECLARE included more than
17,000 patients across 882 sites in 33 countries and was independently
run in collaboration with academic investigators from the TIMI study
group (Boston, USA) and the Hadassah Hebrew University Medical Center
(Jerusalem, Israel).8
DECLARE is part of the extensive DapaCare clinical program for FARXIGA,
whichwill enroll patients in randomized clinical trials,
including a wide range of mechanistic studies, and is supported by a
multinational real-world evidence study (CVD-REAL). The DapaCare
clinical program will generate data across a spectrum of people with CV
risk factors, established CV disease and varying stages of renal
disease, both with and without T2D. DECLARE is paving the way for three
Phase III trials: Dapa-HF, DELIVER and Dapa-CKD.
About AstraZeneca in Cardiovascular, Renal & Metabolism (CVMD)
Cardiovascular,
renal and metabolic diseases together form one of AstraZeneca’s main
therapy areas and platforms for future growth. By following the science
to understand more clearly the underlying links between the heart,
kidney and pancreas, AstraZeneca is investing in a portfolio of
medicines to protect organs and improve outcomes by slowing disease
progression, reducing risks and tackling co-morbidities. Our ambition is
to modify or halt the natural course of CVMD diseases and even
regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and
cardiovascular health for millions of patients worldwide.
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 therapy areas – Oncology, Cardiovascular, Renal &
Metabolism 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 http://www.astrazeneca-us.com and
follow us on Twitter @AstraZenecaUS.
References
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International Diabetes Federation, IDF Diabetes Atlas, Eighth Edition
Update, 2017.
-
Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and
incidence of cardiovascular diseases: a cohort study in 1·9 million
people. Lancet Diabetes Endocrinol. 2015;3:105-113.
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Faden, et al. The increasing detection of asymptomatic left
ventricular dysfunction in patients with type 2 diabetes mellitus
without overt cardiac disease: Data from the SHORTWAVE study. Diabetes
Res Clin Pract. 2013;101(3):309-16.
-
Low Wang, Cecilia C. et al. “Atherosclerotic Cardiovascular Disease
and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and
Clinical Considerations.” Circulation 133.24 (2016): 2459–2502. PMC.
Web. 19 Sept. 2018.
-
Heidenreich, Paul A. et al. “Forecasting the Impact of Heart Failure
in the United States: A Policy Statement From the American Heart
Association.” Circulation. Heart failure 6.3 (2013): 606–619. PMC.
Web. 19 Sept. 2018.
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Nichols GA, Brown JB: The impact of cardiovascular disease on medical
care costs in subjects with and without type 2 diabetes. Diabetes Care
25:482–486, 2002.
-
Nichols, et al. The incidence of congestive heart failure in type 2
diabetes. Diabetes Care, Volume 27, Number 8, August 2004: http://care.diabetesjournals.org/content/27/8/1879.
-
DECLARE - Multicenter Trial to Evaluate the Effect of Dapagliflozin on
the Incidence of Cardiovascular Events(DECLARE-TIMI58). Accessed
September 2018.https://clinicaltrials.gov/ct2/show/NCT01730534.
US-22108
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