FARXIGA showed a 47% reduction in the composite of kidney function
decline, end-stage renal disease or renal death in a pre-specified
analysis from DECLARE-TIMI 58
A pre-specified exploratory analysis of renal data from the Phase
III DECLARE-TIMI 58 trial, the broadest cardiovascular outcomes trial of
a sodium-glucose co-transporter 2 (SGLT2) inhibitor, showed that FARXIGA
(dapagliflozin) reduced the progression of kidney disease or renal death
in patients with type 2 diabetes (T2D).
These data, presented today at the American Diabetes Association (ADA)
79th Scientific Sessions, San Francisco, USA, and simultaneously
published in The
Lancet Diabetes & Endocrinology, showed a 47% reduction
with FARXIGA in the relative risk of the composite renal-specific
outcome of kidney function decline (sustained ≥40% decrease in estimated
glomerular filtration rate [eGFR] to <60 mL/min/1.73m2),
end-stage renal disease (ESRD), or renal death (excluding cardiovascular
death) compared to placebo (1.5% vs. 2.8%; HR 0.53 [95% CI 0.43-0.66]).1
Additionally, FARXIGA reduced the relative risk of a cardio-renal
composite of kidney function decline, ESRD, or renal or cardiovascular
(CV) death by 24% compared to placebo (4.3% vs. 5.6%; HR 0.76 [95% CI
0.67-0.87]).1
This analysis evaluated 17,160 patients with T2D and predominantly
preserved renal function, irrespective of underlying atherosclerotic CV
disease (ASCVD). People with diabetes have a six-to-twelve times higher
risk of developing ESRD and are approximately twice as likely to develop
chronic kidney disease (CKD) than those without.2,3 FARXIGA
is an inhibitor of SGLT2 indicated as an adjunct to diet and exercise to
improve glycemic control in adults with T2D. FARXIGA is not approved to
reduce the risk of renal or CV death, or to slow the progression of
kidney disease.
Elisabeth Björk, Senior Vice President, Head of Late-stage Development,
Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said:
“Heart failure and renal diseases are two of the most common and early
complications experienced by people living with type 2 diabetes, and are
too often overlooked. They contribute to a growing economic burden on
the global healthcare system and can lead to fatal outcomes for
patients. These data continue to offer clinically relevant evidence of
the early cardio-renal effects of FARXIGA.”
While ESRD was a rare event in the trial, the incidence was lower in the
FARXIGA arm compared to placebo (0.1% vs. 0.2%; HR 0.31 [95% CI
0.13 - 0.79]). The renal-specific outcome was consistent across
subgroups regardless of eGFR or urinary albumin-to-creatinine ratio
(UACR) category, whether they had established ASCVD or multiple CV risk
factors.1
These data were presented alongside other clinically important renal
outcomes data from the DECLARE-TIMI 58 trial, including positive results
from another sub-analysis that evaluated UACR, a key marker of kidney
health. FARXIGA improved renal function as measured by changes in UACR
(improved from micro- to normo-albuminuria [HR 1.35, 95% CI
{1.24, 1.47}], improved from macro- to micro- or normo-albuminuria
[HR 1.55, 95% CI {1.34, 1.8}], and decreased deterioration from normo-
to micro- or macro-albuminuria [HR 0.84, 95% CI {0.79, 0.89}]).4
Indication and Limitations of Use for FARXIGA® (dapagliflozin)
tablets
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)
tablets
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 when the eGFR is <45 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
-
Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Rare
but serious, life-threatening cases have been reported in patients
receiving SGLT2 inhibitors including FARXIGA. Cases have been reported
in females and males. Serious outcomes have included hospitalization,
surgeries, and death. Assess patients presenting with pain or
tenderness, erythema, swelling in the genital or perineal area, along
with fever or malaise. If suspected, institute prompt treatment and
discontinue 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 see accompanying US Full
Prescribing Information and Medication
Guide for FARXIGA.
– ENDS –
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).
About DapaCare
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 trials 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, Dapa-CKD and DETERMINE. FARXIGA is not indicated to
reduce the risk of CV events, CV death, or hHF, or the treatment of CKD.
About AstraZeneca in CV, Renal & Metabolism (CVMD)
CV, renal and metabolism together form one of AstraZeneca’s main therapy
areas and a key growth driver for the Company. By following the science
to understand more clearly the underlying links between the heart,
kidneys 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 potentially
regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and CV 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. 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.
References
1. Mosenzon O et al. Effects of dapagliflozin on
development and progression of kidney disease in patients with type 2
diabetes: Analysis from DECLARE-TIMI 58 trial. The Lancet Diabetes &
Endocrinology.
2. Narres M et al. The Incidence of End-Stage
Renal Disease in the Diabetic (Compared to the Non-Diabetic) Population:
A Systematic Review. PLoS ONE 2016; 11(1):e0147329.
3. Koye
DN et al. The Global Epidemiology of Diabetes and Kidney Disease. Adv
Chronic Kidney Dis. 2018; 25(2):121-132.
4. Mosenzon O et al.
Effects of dapagliflozin on the urinary albumin-to-creatinine ratio in
patients with type 2 diabetes: a predefined analysis from the
DECLARE-TIMI 58 randomised, placebo-controlled trial. Oral Presentation
at the American Diabetes Association 79th Scientific
Sessions. (Oral 244-OR, Monday, June 10; 8:15 – 8:30 AM PST)
US-29104 Last Updated 6/19
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