Results reinforce FARXIGA’s potential to
treat a wide range of patients with chronic kidney disease
A new subgroup analysis from the ground-breaking DAPA-CKD Phase
III trial showed that AstraZeneca’s FARXIGA® (dapagliflozin), on
top of standard of care, reduced the composite of worsening of
kidney function or risk of cardiovascular (CV) or renal death in
patients with chronic kidney disease (CKD), irrespective of the
underlying cause of the disease.1
CKD is a serious, progressive condition defined by decreased
kidney function. It is estimated it affects nearly 700 million
people worldwide, many of them still undiagnosed.2–5 The main
causes of CKD are diabetes (38%), high blood pressure (26%), and
glomerulonephritis (kidney inflammation, 16%).6
In the subgroup analysis, compared to placebo, FARXIGA showed a
relative risk reduction (RRR) of 37% for patients whose CKD was
primarily driven by diabetic kidney disease; (absolute risk
reduction [ARR] = −5.8%), 25% for high blood pressure; (ARR =
−2.2%), 57% for glomerulonephritis; (ARR = −7.5%), and 42% for CKD
of other or unknown causes. (p−interaction for RRR 0.53).
Similarly, FARXIGA showed a reduction in all-cause mortality, a
secondary outcome, compared to placebo, regardless of underlying
CKD cause (p-interaction 0.55).7
The safety and tolerability of FARXIGA was consistent with the
well-established safety profile of the medicine.
Prof. Hiddo L. Heerspink, Co-chair of the DAPA-CKD trial and its
Executive Committee, University Medical Center Groningen, the
Netherlands, said: “These results reinforce the potential of
FARXIGA to change the standard of care for a wide range of patients
with chronic kidney disease, regardless of the root cause of their
disease. This could open up enormous possibilities for the millions
of patients living with chronic kidney disease worldwide.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: “The DAPA-CKD trial showed the potential of FARXIGA
as the first SGLT2 inhibitor to significantly prolong survival in a
renal outcomes trial in patients with chronic kidney disease with
and without type 2 diabetes. The new data presented further
demonstrate FARXIGA’s consistent and clinically meaningful benefit
across a diverse group of patients with chronic kidney disease, a
population in urgent need of new treatment options to slow the
progression of their disease.”
The data were presented at the American Society of Nephrology
(ASN) Kidney Week Reimagined 2020.
Earlier this month, FARXIGA was granted Breakthrough Therapy
Designation by the US Food and Drug Administration (FDA) for
patients with CKD, with and without T2D. Additionally, in May 2020,
FARXIGA was approved in the US to reduce the risk of CV death and
hospitalization for heart failure (hHF) in adults with heart
failure (NYHA class II-IV) with reduced ejection fraction (HFrEF)
with and without T2D.
In the US, FARXIGA is also indicated as an adjunct to diet and
exercise to improve glycemic control in adults with T2D and to
reduce the risk of hospitalization for heart failure in patients
with T2D and established CV disease or multiple CV risk factors.
FARXIGA is not indicated to reduce the worsening of renal function
or death in patients with CKD.
INDICATIONS 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
- to reduce the risk of hospitalization for heart failure in
adults with type 2 diabetes mellitus and established cardiovascular
(CV) disease or multiple CV risk factors
- to reduce the risk of cardiovascular death and hospitalization
for heart failure in adults with heart failure (NYHA class II-IV)
with reduced ejection fraction
FARXIGA is not recommended for patients with type 1 diabetes
mellitus or for the treatment of diabetic ketoacidosis.
IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5
mg and 10 mg tablets
Contraindications
- Prior serious hypersensitivity reaction to FARXIGA
- Patients with severe renal impairment (eGFR <30 mL/min/1.73
m2) being treated for glycemic control without established CV
disease or multiple CV risk factors
- Patients on dialysis
Warnings and Precautions
- Volume Depletion: FARXIGA can cause intravascular volume
depletion which may manifest as symptomatic hypotension or acute
transient changes in creatinine. Acute kidney injury requiring
hospitalization and dialysis has been reported in patients with
type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA.
Patients with impaired renal function (eGFR less than 60
mL/min/1.73 m2), elderly patients, or patients on loop diuretics
may be at increased risk for volume depletion or hypotension.
Before initiating FARXIGA in these patients, assess volume status
and renal function. After initiating therapy, monitor for signs and
symptoms of hypotension and renal function
- Ketoacidosis in Diabetes Mellitus 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
- 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 with diabetes mellitus 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
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
DOSING
- To improve glycemic control in patients with T2D, the
recommended starting dose of FARXIGA is 5 mg orally once daily,
taken in the morning. In patients tolerating FARXIGA 5 mg once
daily who require additional glycemic control, the dose can be
increased to 10 mg once daily
- To reduce the risk of hospitalization for heart failure in
patients with T2D and established CV disease or multiple CV risk
factors, the recommended dose of FARXIGA is 10 mg orally once
daily
- To reduce the risk of CV death and hospitalization for heart
failure in patients with HFrEF, the recommended dose of FARXIGA is
10 mg orally once daily
Please see accompanying US Full Prescribing Information and
Medication Guide for FARXIGA.
Chronic kidney disease
CKD is a serious, progressive condition defined by decreased
kidney function (shown by reduced estimated glomerular filtration
rate [eGFR] or markers of kidney damage, or both, for at least
three months).2–5 In its most severe form, known as end stage
kidney disease (ESKD), kidney damage and deterioration of kidney
function have progressed to the stage where dialysis or kidney
transplantation are required.8 The majority of patients with CKD
will die from CV causes before reaching ESKD.9
DAPA-CKD
DAPA-CKD is an international, multi-center, randomized,
double-blinded trial in 4,304 patients designed to evaluate the
efficacy of FARXIGA 10 mg, compared with placebo, in patients with
CKD Stages 2-4 and elevated urinary albumin excretion, with and
without T2D. FARXIGA was given once daily in addition to standard
of care. Detailed results shared at the European Society of
Cardiology Meeting in August 2020 and published in The New England
Journal of Medicine showed FARXIGA reduced the primary composite
endpoint of worsening of renal function (defined as a composite of
a sustained ≥50% eGFR decline, onset of ESKD and death from CV or
renal cause) or renal or CV death by 39% compared to placebo
(p<0.0001). The results were consistent in patients both with
and without T2D. FARXIGA also met all secondary endpoints including
the time to first occurrence of the renal composite (sustained ≥50%
eGFR decline, ESKD and renal death), the composite of CV death or
hHF, and death from any cause by 31% (ARR = 2.1%, p=0.0035). Median
duration of the study was 2.4 years.
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.
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 & Immunology. 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
- Wheeler D. Effects of dapagliflozin on kidney function,
cardiovascular events and all-cause mortality according to cause of
kidney disease in the DAPA-CKD trial. (presented at the American
Society of Nephrology - Kidney Week 2020 Reimagined. 22-25 October
2020).
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work
Group. KDIGO 2012 clinical practice guideline for the evaluation
and management of chronic kidney disease. Kidney International
Supplement. 2013;(3):1–150.
- Bikbov B et al. Global, regional, and national burden of
chronic kidney disease, 1990–2017: A systematic analysis for the
Global Burden of Disease Study 2017. The Lancet. 2020;
395(10225):709–33.
- Hirst JA et al. Prevalence of chronic kidney disease in the
community using data from OxRen: A UK population-based cohort
study. Br J Gen Pract. 2020;70(693):e285-e293.
- National Kidney Foundation. Kidney Disease: The Basics; 2020
[cited 23 September 2020]. Available from: URL:
https://www.kidney.org/news/newsroom/factsheets/KidneyDiseaseBasics.
- National Kidney Foundation. Kidney Disease: Causes; 2015 [cited
23 September 2020]. Available from: URL:
https://www.kidney.org/atoz/content/kidneydiscauses.
- Heerspink HJL et al. Dapagliflozin in Patients with Chronic
Kidney Disease. N Engl J Med. 2020;383(15):1436-1446.
- Centers for Disease Control and Prevention (CDC). Chronic
Kidney Disease in the United States, 2019; 2019 [cited 31 March
2020]. Available from: URL:
https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.html
- Briasoulis A, Bakris GL. Chronic Kidney Disease as a Coronary
Artery Disease Risk Equivalent. Current Cardiology Reports.
2013;15(3):340.
US-46365 Last Updated 10/20
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