FARXIGA Achieved a Positive Result in the Phase III DECLARE-TIMI 58 Trial, a Large Cardiovascular Outcomes Trial in 17,000 Pa...
September 24 2018 - 7:00AM
Business Wire
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
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 Bj�rk, Vice President, Head of Cardiovascular, Renal
and Metabolism, Global Medicines Development at AstraZeneca said:
“FARXIGA has 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, which will 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 AstraZenecaAstraZeneca 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
- 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.
- 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.
- 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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