a4731x
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of August 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Farxiga reduced risk of CV death or worsening HF
30 August 2022 07:00 BST
Farxiga significantly
reduced the risk of cardiovascular death or worsening of heart
failure in patients with mildly reduced or preserved ejection
fraction in DELIVER Phase III trial
Results presented at European Society of Cardiology Congress 2022,
and published in New England Journal of Medicine
Data extend the clinically meaningful benefits of Farxiga in
patients with heart failure regardless of ejection
fraction
Heart failure is a chronic, progressive disease impacting nearly 64
million people
Detailed results from the DELIVER Phase III trial showed
AstraZeneca's Farxiga (dapagliflozin) significantly reduced the
composite of cardiovascular (CV) death or worsening heart failure
(HF) in patients with HF and mildly reduced or preserved ejection
fraction (EF), compared to placebo. The results were presented
today at the European Society of Cardiology Congress 2022 in
Barcelona, Spain, and simultaneously published
in The
New England Journal of Medicine1.
Farxiga reduced the
composite outcome of CV death or worsening of HF by 18%
(p<0.001, 16.4% in the dapagliflozin group and 19.5% in the
placebo group over a median follow-up of 2.3 years). All individual
components contributed to the superiority of the primary endpoint.
The findings were consistent across key subgroups examined and
extend the benefits of Farxiga to the full spectrum of patients with
HF irrespective of left ventricular ejection fraction (LVEF)
status. The trial results also showed a symptom benefit in
patient-reported outcomes measured by the Kansas City
Cardiomyopathy Questionnaire (KCCQ) total symptom
score1.
Dr. Scott Solomon, Professor of Medicine at Harvard Medical School
and Brigham and Women's Hospital and Principal Investigator of the
DELIVER Phase III trial, said: "These results from DELIVER are
important for patients and clinical care as it
shows that dapagliflozin is effective regardless of
ejection fraction and therefore can be used as foundational therapy
in all eligible patients with heart failure. Earlier HFpEF
trials have shown attenuation in the highest LVEF but with
dapagliflozin results are consistent across the LVEF
range. The findings also reinforce most recent treatment
guidelines, recommending earlier initiation of guideline-directed
medical treatment and may support broader use of SGLT2 inhibitors
in clinical practice."
The updated 2022 joint HF guidelines issued by the American College
of Cardiology, the American Heart Association and the Heart Failure
Society of America, now recommend sodium-glucose cotransporter 2
(SGLT2) inhibitors such as Farxiga for HF with mildly reduced EF (HFmrEF) and
HF with preserved EF (HFpEF). This expands upon previous
recommendations supporting the use of SGLT2 inhibitors in HF with
reduced EF (HFrEF)2.
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said:
"Heart failure patients with LVEF greater than 40% are the most
difficult to treat with few treatment options available to them. We
are proud to share the groundbreaking DELIVER results, which have
expanded our understanding of the complexities of HF. These data
build upon our previous studies demonstrating cardiorenal
protection of Farxiga across patients with type-2 diabetes,
chronic kidney disease and heart failure."
DELIVER was designed with broader inclusion criteria than prior
trials in this patient population to also include patients who were
hospitalised, recently hospitalised, or those with HF with improved
LVEF, for whom evidence-based therapy is limited1,2. These
findings build upon the previously reported results from DAPA-HF,
the only SGLT2 inhibitor outcomes trial in HF to demonstrate a
significant reduction in mortality, to provide further evidence to
support the use of Farxiga as foundational therapy for patients with
HF, regardless of ejection fraction.
The safety and tolerability profile of Farxiga in the DELIVER Phase III trial was
consistent with the well-established safety profile of the
medicine.
Notes
HF
HF is a chronic, long-term condition that worsens over
time3.
It affects nearly 64 million people globally and is associated
with substantial morbidity and mortality4,5. Chronic
HF is the leading cause of hospitalisation for those over the age
of 65 and represents a significant clinical and economic
burden6.
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%)2.
Approximately half of all HF patients have HFmrEF or HFpEF, with
few therapeutic options available2,7.
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 standard of care [SoC] for all
comorbidities, including diabetes and hypertension, with the
exception of concomitant use of a SGLT2
inhibitor)8.DELIVER
is the largest clinical trial to date in HF patients with LVEF
above 40%, with 6,263 randomised patients8,9.
The primary endpoint was the time to first occurrence of CV death,
hospitalisation for HF (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
cause8.
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
pancreas10-12.
Damage to one of these organs can cause the other organs to fail,
contributing to leading causes of death worldwide, including type-2
diabetes (T2D), HF and chronic kidney disease
(CKD)4,13-15.
Farxiga is approved for
adults and children aged 10 years and above for the treatment of
insufficiently controlled T2D 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 and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Solomon S, et al.
Dapagliflozin in Heart Failure with Mildly Reduced or Preserved
Ejection Fraction. N Engl J
Med 2022
[cited 2022 Aug 27] Available from: www.nejm.org/doi/full/10.1056/NEJMoa2206286
2. 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.
3. Cleveland
Clinic [Internet]. Heart failure; [cited 2022 Jul 26] Available
from: https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure
4. 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.
5. Mozaffarian D, et al. Heart
disease and stroke statistics-2016 update. Circulation. 2016; 133(4):e38-360.
6. Azad N, et al. Management of
chronic heart failure in the older
population. J Geriatr
Cardiol. 2014;
11(4):329-37.
7. Dunlay SM, et al. Epidemiology
of heart failure with preserved ejection
fraction. Nat Rev
Cardiol 2017;14(10):591-602.
8. 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.
9. Clinicaltrials.gov
[Internet]. Dapagliflozin Evaluation to Improve the LIVEs of
Patients With Preserved Ejection Fraction Heart Failure; [cited
2022 Jul 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT03619213.
10. McMurray JJV, et al. Dapagliflozin in
patients with heart failure and reduced ejection
fraction. N Engl J
Med 2019;
381(21):1995-2008.
11. Heerspink HJL, et al. Dapagliflozin in
patients with chronic kidney disease. N Engl J
Med 2020;
383(15):1436-46.
12. 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.
13. Mayo Clinic [Internet].
Heart failure, 2020; [cited 2022 Jul 26]. Available
from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
14. Centers for Disease
Control and Prevention (CDC) [Internet]. A snapshot: Diabetes in
the United States, 2020; [cited 2022 Jul 26]. Available
from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.
15. National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet].
Heart disease & kidney disease, 2016; [cited 2022 Jul 26].
Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
30 August 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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