Data were consistent in patients with and
without type 2 diabetes, showed early effects in the first month
and improvement in patient-reported outcomes
AstraZeneca today announced new data from five additional
analyses of the landmark Phase III DAPA-HF trial, which showed that
FARXIGA (dapagliflozin) reduced the risk of the primary composite
outcome of worsening heart failure (HF), defined as hospitalization
or an urgent visit, or death from cardiovascular (CV) causes versus
placebo, when added to standard of care.
DAPA-HF is the first outcomes trial with an SGLT2 inhibitor
investigating the treatment of HF in patients with reduced ejection
fraction (HFrEF), with and without type 2 diabetes (T2D). The new
analyses showed the consistency of these results across patient
subgroups with and without T2D, an early onset of effects, and
improvement in patient-reported outcomes of HF-related health
status.
These data were presented at the American Heart Association
(AHA) Scientific Sessions in Philadelphia.
Elisabeth Bj�rk, Senior Vice President, Head of Late-stage
Development, Cardiovascular, Renal and Metabolism,
BioPharmaceuticals R&D, said: “Heart failure affects
approximately 64 million people around the world and about half of
those patients will die within five years of diagnosis. These new
analyses from the DAPA-HF trial reinforce the science behind
FARXIGA as clinically significant across heart failure patient
populations and suggest the potential to improve the current
standard of care for millions of these patients.”
Across all five analyses, FARXIGA showed improvements versus
placebo in the worsening or progression of the disease and improved
patient-reported symptoms and quality of life.
The Dapagliflozin and Prevention of Adverse-outcomes in Heart
Failure Trial (DAPA-HF): Results in Nondiabetic Patients subgroup
analysis showed that FARXIGA reduced the risk of the primary
composite endpoint compared to placebo in patients with HFrEF
without T2D. This analysis evaluated the primary composite and its
components and secondary endpoints in a subgroup of patients
without T2D. With FARXIGA, the relative risk of the composite of
worsening of HF or CV death was reduced by 27% among participants
without diabetes (absolute risks 9.2% vs 12.7%, n=2605; HR 0.73
[95% CI 0.60, 0.88]) and by 25% in patients with diabetes (14.6% vs
19.4%, n=2139; HR 0.75 [95% CI 0.63, 0.90]). All components
contributed to the overall result. The data suggest that FARXIGA
has the potential to be a treatment for patients with HFrEF both
with and without T2D.
Another pre-specified analysis presented, Effect of Treatment on
the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the
Dapagliflozin And Prevention Of Adverse-outcomes In Heart Failure
Trial (DAPA-HF), examined the effects of FARXIGA on HF related
health status (symptoms, physical limitations and quality of life)
in HFrEF, assessed using the KCCQ. An improvement in the KCCQ total
score for dapagliflozin compared to placebo was seen at 4 months,
and the magnitude of the improvement was amplified at 8 months.
Furthermore, fewer patients treated with FARXIGA had significant
deterioration (≥5 points), and more experienced small (≥5 points),
moderate (≥10 points) and large (≥15 points) clinically meaningful
improvements in total KCCQ score. The total symptom score on the
KCCQ range from 0 to 100, with higher scores indicating fewer
symptoms and physical limitations associated with HF and a change
of 5 or more points considered to be clinically meaningful.
The Timing of Onset of Clinical Benefit with Dapagliflozin in
Patients with Heart Failure: An Analysis from the Dapagliflozin And
Prevention of Adverse-outcomes In Heart Failure Trial (DAPA-HF)
post-hoc analysis explored the timing of onset of clinical benefit
with FARXIGA in patients with HFrEF compared to placebo. Reduction
in the risk of the composite of worsening HF or CV death versus
placebo was shown as soon as 4 weeks. These exploratory data
reinforce that FARXIGA provided crucial early benefit for patients
with HF.
The Effect of Treatment According to Age in the Dapagliflozin
And Prevention Of Adverse-outcomes In Heart Failure Trial (DAPA-HF)
subgroup analysis suggested that FARXIGA may benefit outcomes in
patients with HFrEF, regardless of age. There was no apparent
effect of age on the occurrence of adverse events or treatment
discontinuation of dapagliflozin versus placebo.
The Influence of Ejection Fraction on the Effect of Treatment in
the Dapagliflozin And Prevention Of Adverse-outcomes In Heart
Failure Trial (DAPA-HF) subgroup analysis indicated that the
treatment effects of dapagliflozin versus placebo were consistent
over a broad spectrum of left ventricular ejection fraction (LVEF)
(P interaction = 0.205 for primary composite outcome). LVEF is a
predictor of mortality and hospitalization related to HF.
These positive FARXIGA results build on the DAPA-HF detailed
results announced in September 2019. FARXIGA is currently being
studied in patients with HF with preserved ejection fraction
(HFpEF) in the DELIVER and DETERMINE (HFrEF and HFpEF) trials.
Additionally, in September 2019, the US Food and Drug
Administration (FDA) granted Fast Track designation for FARXIGA to
reduce the risk of CV death, or the worsening of HF in adults with
HFrEF or HFpEF based on the Phase III DAPA-HF and DELIVER trials.
The FDA also recently updated the FARXIGA label to add an
indication to reduce the risk of hospitalization for HF (hHF) in
adults with T2D and established CV disease or multiple CV risk
factors. The approval was based on results from the landmark
DECLARE-TIMI 58 CV outcomes trial (CVOT), the largest SGLT2
inhibitors CVOT conducted to date. FARXIGA is not indicated to
reduce the risk of hHF in patients without diabetes, or to reduce
the risk of CV death.
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
- to reduce the risk of hospitalization for heart failure in
adults with type 2 diabetes mellitus and established cardiovascular
disease or multiple cardiovascular risk factors
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: FARXIGA causes intravascular volume
contraction and can cause acute kidney injury. Reports of acute
kidney injury requiring hospitalization and dialysis have occurred
with FARXIGA. If acute kidney injury occurs, discontinue and
promptly treat
Increases in serum creatinine and decreases in eGFR may be
observed with initiation of FARXIGA. Elderly patients and patients
with impaired renal function may be more susceptible to these
changes. Consider temporarily discontinuing in settings of reduced
oral intake or fluid losses
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
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 DAPA-HF
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in
Heart Failure) is an international, multicenter, parallel group,
randomized, double-blind trial in patients with heart failure and
reduced ejection fraction (LVEF ≤ 40%), with and without T2D,
designed to evaluate the effect of FARXIGA 10mg, compared with
placebo, given once daily in addition to standard of care. The
primary composite outcome was time to a worsening heart failure
event (hospitalization or equivalent event; i.e. an urgent heart
failure visit), or cardiovascular death.
The full results of the DAPA-HF trial were published in The New
England Journal of Medicine in September 2019.
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.
US-34678 Last Updated 11/19
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