REG - AstraZeneca PLC - Farxiga shows CV mortality benefit across EF range

AstraZenecaAnnouncement

30/08/2022 07:15

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RNS Number : 4513X  AstraZeneca PLC  30 August 2022

30 August 2022 07:01 BST

 

New data show Farxiga significantly lowers the risk of cardiovascular death in
patients with heart failure

 

Pre-specified pooled analysis from Phase III trials demonstrated reduction in
CV death by 14% and reduction in death from any cause by 10% in patients with
heart failure irrespective of ejection fraction

 

First heart failure medication to demonstrate mortality benefit across the
full ejection fraction range

 

Results being presented at the European Society of Cardiology annual meeting
and simultaneously published in Nature Medicine

 

Today, new results from a pre-specified, patient level, pooled analysis from
the Phase III DAPA-HF and DELIVER trials demonstrated mortality benefit of
Farxiga (dapagliflozin), compared to placebo, in patients with heart failure
(HF). These results were presented at the European Society of Cardiology
Congress 2022 in Barcelona, Spain and simultaneously published in Nature
Medicine(1). The reduction in risk of cardiovascular (CV) death was consistent
across pre-specified subgroups and is the first analysis to demonstrate a
mortality benefit with a HF medication in patients with HF across the left
ventricular ejection fraction (LVEF) range.

 

The analysis showed that Farxiga reduced the risk of CV death by 14% (p=0.01,
absolute risk reduction  ARR  1.5%) over the median follow-up of 22 months,
death from any cause by 10% (p=0.03, ARR 1.5%), total (first and repeat)
hospitalisation for HF by 29% (p < 0.001, ARR 6%), and the composite of
death from CV causes, myocardial infarction, or stroke by 10% (p=0.045, ARR
1.3%), in patients with HF irrespective of LVEF(1).

 

Prof. John McMurray, Professor of Medical Cardiology and Deputy Director of
the Institute of Cardiovascular and Medical Sciences at the University of
Glasgow, UK, said: "In this patient-level meta-analysis including over 11,000
patients with heart failure across the full range of ejection fraction,
dapagliflozin reduced the risk of both cardiovascular death and heart failure
hospitalisation. These results underpin the valuable role dapagliflozin can
play in clinical practice, as we can initiate treatment right away while
waiting for ejection fraction to be measured."

 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said:

"Heart failure remains one of the leading causes of death worldwide with high
unmet need for some 64 million people. This analysis demonstrates Farxiga's
ability to treat patients across the full left ventricular ejection fraction
spectrum and reduce the risk of cardiovascular death."

 

The DAPA-HF and DELIVER Phase III trials were randomised and double-blind,
comparing Farxiga to placebo. Each trial enrolled patients with a diagnosis of
HF, functional limitation, and elevated natriuretic peptides. The principal
difference between the two trials was that patients with an LVEF of 40% or
less were randomised in DAPA-HF and those with a LVEF greater than 40% in
DELIVER(3,4). The studies included 11,007 individuals with HF across 20
countries in each trial.

 

Notes

 

HF
HF is a chronic, long-term condition that worsens over time(5). It affects
nearly 64 million people globally and is associated with substantial morbidity
and mortality(6,7). Chronic HF is the leading cause of hospitalisation for
those over the age of 65 and represents a significant clinical and economic
burden(8). 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: HF with reduced EF (HFrEF, LVEF less than or equal to 40%), HF with
mildly reduced EF (HFmrEF, LVEF 41-49%) and HF with preserved EF (HFpEF, LVEF
greater than or equal to 50%)(9). Approximately half of all HF patients have
HFmrEF or HFpEF, with few therapeutic options available(9,10).

DAPA-HF
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure)
was an international, multi-centre, parallel-group, randomised, double-blinded
Phase III trial in 4,744 patients with HFrEF, with and without type-2 diabetes
(T2D), designed to evaluate the effect of Farxiga 10mg, compared with
placebo, given once daily in addition to standard of care (SoC) consisting of
an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor
blocker (ARB). The primary composite endpoint was time to the first occurrence
of a worsening HF event (hospitalisation or equivalent event, i.e. an urgent
HF visit), or CV death. The median duration of follow-up was 18.2 months(2,4).

The secondary endpoint included the total number of hospitalisations for HF
(hHF, including repeat admissions) and CV deaths, change from baseline to 8
months in the total symptom score on the Kansas City Cardiomyopathy
Questionnaire (KCCQ)(4).

DELIVER
DELIVER was an international, randomised, 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)(3).DELIVER is the largest
clinical trial to date in HF patients with LVEF above 40%, with 6,263
randomised patients(1,3).

 

The primary endpoint was the time to first occurrence of CV death, hHF or an
urgent HF visit. The secondary endpoint includes 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(3).

 

Farxiga

Farxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor.
Research has shown Farxiga's efficacy in preventing and delaying cardiorenal
disease, while also protecting the organs - important findings given the
underlying links between the heart, kidneys and pancreas(4,11,12.) Damage to
one of these organs can cause the other organs to fail, contributing to
leading causes of death worldwide, including T2D, HF and chronic kidney
disease (CKD)(6,13-15).

 

Farxiga is approved in adults and children aged 10 years and above for the
treatment of insufficiently controlled type-2 diabetes mellitus as an adjunct
to diet and exercise. Farxiga is also approved for the treatment of HFrEF and
the treatment of CKD based on the findings of the DAPA-HF and DAPA-CKD Phase
III trials.

 

DapaCare is a robust programme of clinical trials to evaluate the potential
CV, renal and organ protection benefits of Farxiga. It includes more than 35
completed and ongoing Phase IIb/III trials in more than 35,000 patients, as
well as more than 2.5 million patient-years' experience. Farxiga is currently
being tested in patients without T2D following an acute myocardial infarction
or heart attack in the DAPA-MI Phase III trial - a first of its kind,
indication-seeking registry-based randomised controlled trial.

 

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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation 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.com (https://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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.

 

References

1.   Jhund P, et al. Dapagliflozin and outcomes across the range of ejection
fraction in patients with heart failure: a patient-level pooled analysis of
DAPA-HF and DELIVER. Nature Medicine [cited 2022 Aug 27] Available from:
https://www.nature.com/articles/s41591-022-01971-4
(https://protect-de.mimecast.com/s/2gcOCLZj2GtN9roJvsB1pZb?domain=nature.com)

2.   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):1217-25.

3.     McMurray JJV, et al. Dapagliflozin in patients with heart failure
and reduced ejection fraction. N Engl J Med 2019; 381(21):1995-2008.

4.   Cleveland Clinic  Internet . Heart failure; [cited 2022 Jul 14]
Available
from: https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure
(https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure)

5.   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):1211-59.

6.   Mozaffarian D, et al. Heart disease and stroke statistics-2016
update. Circulation. 2016; 133(4):e38-360.

7.   Azad N, et al. Management of chronic heart failure in the older
population. J Geriatr Cardiol. 2014; 11(4):329-37.

8.   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.

9.   Dunlay SM, et al. Epidemiology of heart failure with preserved ejection
fraction. Nat Rev Cardiol 2017;14(10):591-602.

10.  Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney
disease. N Engl J Med 2020; 383(15):1436-46.

11.  Wiviott SD, et al. for the DECLARE-TIMI 58 Investigators. Dapagliflozin
and cardiovascular outcomes in type-2 diabetes [article and supplementary
appendix]. N Engl J Med 2019; 380(4):347-57.

12.  Mayo Clinic  Internet . Heart failure, 2020; [cited 2022 Jul 14].
Available
from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142
(https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142)
.

13.  Centers for Disease Control and Prevention (CDC)  Internet . A snapshot:
Diabetes in the United States, 2020; [cited 2022 Jul 14]. Available
from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html
(https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html)
.

14.  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 Internet . Heart disease & kidney disease, 2016; [cited 2022 Jul 14].
Available
from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease
(https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease) .

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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