FDA approval means patients with heart
failure can benefit from FARXIGA regardless of left
ventricular ejection fraction status
AstraZeneca’s FARXIGA (dapagliflozin) has been approved in the
US to reduce the risk of cardiovascular (CV) death, hospitalization
for heart failure (hHF) and urgent heart failure (HF) visits in
adults with HF. The approval by the Food and Drug Administration
(FDA) was based on positive results from the DELIVER Phase III
trial.1 FARXIGA was previously approved in the US for adults with
HF with reduced ejection fraction (HFrEF).
Ruud Dobber, Executive Vice-President, BioPharmaceuticals
Business Unit, AstraZeneca, said: “Approximately half of heart
failure patients die within five years of diagnosis, highlighting
an urgent unmet need for well-tolerated treatment options that can
bring life-saving benefits and reduce the risk of cardiovascular
death. The approval of FARXIGA in the US not only reinforces
AstraZeneca’s commitment to reducing the burden of this complex and
life-threatening disease, but will help patients across the full
spectrum of heart failure lead healthier lives.”
HF is a chronic, long-term condition that worsens over time2 and
affects almost seven million people in the US.3 It is also the
leading cause of hospitalization for those over 65 years and
represents a significant clinical and economic burden.4
Approximately half of all HF patients have HF with mildly reduced
ejection fraction (HFmrEF) or HF with preserved ejection fraction
(HFpEF)5 and these patients are not only at greater risk of death
and hospitalizations but experience an especially high burden of
symptoms and physical limitations, and a poor quality of life.6
The data from the DELIVER Phase III trial, published in The New
England Journal of Medicine, showed FARXIGA reached a statistically
significant and clinically meaningful early reduction in the
primary composite endpoint of CV death or worsening HF in patients
with HF with HFmrEF or HFpEF.1 The results from a pre-specified,
pooled analysis of the DAPA-HF and DELIVER Phase III trials,
published in Nature Medicine, showed that the treatment effect of
FARXIGA on the composite endpoint of cardiovascular death,
hospitalization for heart failure or urgent heart failure was
consistent across the left ventricular ejection fraction (LVEF)
range and established FARXIGA as the first sodium-glucose
cotransporter 2 (SGLT2) inhibitor to demonstrate a mortality
benefit.7
FARXIGA is approved for the treatment of patients with type 2
diabetes (T2D), HFrEF and chronic kidney disease (CKD) in more than
100 countries around the world including the US, the European Union
(EU), China and Japan. It has most recently received regulatory
approvals in the EU, Great Britain, Japan and Turkey to extend the
HF indication to include patients across the full LVEF range.
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 either established
cardiovascular (CV) disease or multiple CV risk factors
- to reduce the risk of cardiovascular death, hospitalization for
heart failure, and urgent heart failure visit in adults with heart
failure
- to reduce the risk of sustained eGFR decline, end‑stage kidney
disease, cardiovascular death, and hospitalization for heart
failure in adults with chronic kidney disease at risk of
progression
FARXIGA is not recommended for patients with type 1 diabetes
mellitus. It may increase the risk of diabetic ketoacidosis in
these patients.
FARXIGA is not recommended for use to improve glycemic control
in adults with type 2 diabetes mellitus with an eGFR less than 45
mL/min/1.73 m2. FARXIGA is likely to be ineffective in this setting
based upon its mechanism of action.
FARXIGA is not recommended for the treatment of chronic kidney
disease in patients with polycystic kidney disease or patients
requiring or with a recent history of immunosuppressive therapy for
kidney disease. FARXIGA is not expected to be effective in these
populations.
DOSING
To improve glycemic control, the recommended starting dose is 5
mg orally once daily. Dose can be increased to 10 mg orally once
daily for additional glycemic control.
For all other indications, the recommended dose is 10 mg orally
once daily.
IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5
mg and 10 mg tablets
Contraindications
Prior serious hypersensitivity reaction to FARXIGA
Warnings and Precautions
- Ketoacidosis in Diabetes Mellitus: has been
reported in patients with type 1 and type 2 diabetes receiving
FARXIGA. In placebo-controlled trials of patients with type 1
diabetes, the risk of ketoacidosis was increased in patients who
received SGLT2 inhibitors compared to patients who received
placebo. 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
- 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
- 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
Please see link to US Full Prescribing Information
for FARXIGA.
Notes
HF
HF is a chronic, long-term condition that worsens over time.2 It
affects nearly 64 million people globally8 and is associated with
substantial morbidity and mortality.9 Chronic HF is the leading
cause of hospitalization for those over the age of 65 and
represents a significant clinical and economic burden.4 There are
several types of HF often defined by LVEF, a measurement of the
percentage of blood leaving the heart each time it contracts,
including: HFrEF (LVEF less than or equal to 40%), HFmrEF (LVEF
41-49%) and HFpEF (LVEF greater than or equal to 50%).10
Approximately half of all HF patients have HFmrEF or HFpEF,5 with
few therapeutic options available.6
DELIVER
DELIVER was an international, randomized, double-blind,
parallel-group, placebo-controlled, event-driven Phase III trial
designed to evaluate the efficacy of FARXIGA, compared with
placebo, in the treatment of HF patients with LVEF greater than
40%, with or without T2D. FARXIGA was given once daily in addition
to background therapy (regional SoC for all comorbidities,
including diabetes and hypertension, with the exception of
concomitant use of a sodium-glucose cotransporter 2 (SGLT2)
inhibitor). DELIVER is the largest clinical trial to date in HF
patients with LVEF above 40%, with 6,263 randomized patients.11
The primary composite endpoint was the time to first occurrence
of CV death, hHF or an urgent HF visit. Key secondary endpoints
include the total number of HF events (hHF or urgent HF visit) and
CV death, change from baseline in the total symptom score of the
KCCQ at eight months, time to the occurrence of CV death and time
to the occurrence of death from any cause.11
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of
BioPharmaceuticals, forms one of AstraZeneca’s main disease areas
and is 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 for organ protection and improving outcomes
by slowing disease progression, reducing risks and tackling
co-morbidities. The Company’s ambition is to modify or halt the
natural course of CVRM 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 in Oncology, Rare Diseases, and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. Please visit
astrazeneca-us.com and follow the Company on Twitter
@AstraZenecaUS.
US Media Mailbox: usmediateam@astrazeneca.com
References
- Solomon S, et al. Dapagliflozin in heart failure with mildly
reduced or preserved ejection fraction. N Engl J Med. 2022;
387(12):1089-1098.
- Cleveland Clinic [Internet]. Heart failure [cited 2023 Mar 14].
Available from:
https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure.
- Tsao C., et al. Heart Disease and Stroke Statistics—2022
Update: A Report From the American Heart Association. Circulation.
2023;144(8):e7, e431-444.
- Azad N, et al. Management of chronic heart failure in the older
population. J Geriatr Cardiol. 2014;11(4):329-337.
- McDonagh T, et al. 2021 ESC Guidelines for the diagnosis and
treatment of acute and chronic heart failure. Eur Heart J.
2021;00:1-128.
- Kosiborod MN, et al. The effects of dapagliflozin on symptoms,
function and quality of life in patients with heart failure and
mildly reduced or preserved ejection fraction: results from the
DELIVER Trial. Presented at: American Heart Association (AHA)
Scientific Sessions 2022, 5-7 November 2022, Chicago, Illinois,
USA.
- Jhund P, et al. Dapagliflozin across the range of ejection
fraction in patients with heart failure: a patient-level, pooled
meta-analysis of DAPA-HF and DELIVER. Nat Med. 2022;
28(9):1956-1964.
- Vos T, et al. Global, regional, and national incidence,
prevalence, and years lived with disability for 328 diseases and
injuries for 195 countries, 1990–2016: A systematic analysis for
the Global Burden of Disease Study 2016. Lancet.
2017;390(10100):1211-1259.
- Mozaffarian D, et al. Heart Disease and Stroke Statistics-2016
Update: A Report From the American Heart Association. Circulation.
2016;133(4):e38-360.
- Heidenreich PA et al. 2022 AHA/ACC/HFSA Guideline for the
Management of Heart Failure: A report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical
Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-421.
- Solomon SD, et al. Dapagliflozin in heart failure with
preserved and mildly reduced ejection fraction: rationale and
design of the DELIVER trial. Eur J Heart Fail.
2021;23(7):1217-1225
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