a4269k
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 May 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Farxiga HFpEF Phase III trial met primary endpoint
5 May 2022 07:05 BST
Farxiga met primary endpoint in DELIVER Phase III
trial, reducing risk of cardiovascular death or worsening heart
failure in patients with preserved ejection
fraction
Results from the DELIVER and DAPA-HF Phase III trials demonstrate
Farxiga's efficacy in heart failure regardless of ejection
fraction
High-level results from the DELIVER Phase III trial showed
AstraZeneca's Farxiga (dapagliflozin) reached a statistically
significant and clinically meaningful reduction in the primary
composite endpoint of cardiovascular (CV) death or worsening heart
failure (HF). The trial was conducted in
patients with HF with
mildly reduced or preserved ejection fraction (defined as left
ventricular ejection fraction [LVEF] greater than
40%).
HF is a chronic, long-term condition that worsens over
time1.
It affects nearly 64 million people globally2 and is
associated with substantial morbidity and
mortality3. There
are several main categories of HF related to ejection fraction
(EF), 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 preserved EF (HFpEF)
(LVEF greater than or equal to 50%)4.
Approximately half of all HF patients have mildly reduced or
preserved EF with few therapeutic options
available4,5. Farxiga already
has approved indications relating to the treatment of type-2
diabetes (T2D), HFrEF and chronic kidney disease
(CKD).
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: "We are delighted to have met the
primary endpoint in this patient population which has few treatment
options. DELIVER is the largest and broadest trial to date in heart
failure with mildly reduced or preserved ejection fraction. The
results of DELIVER extend the benefit of dapagliflozin to the full
spectrum of patients with heart failure."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "Today's groundbreaking results coupled
with those from the DAPA-HF trial show
that Farxiga is
effective in treating heart failure regardless of ejection
fraction. These data build upon our previous studies demonstrating
cardiorenal protection across patients with either diabetes,
chronic kidney disease or heart failure."
The safety and tolerability profile of Farxiga in the DELIVER Phase III trial were
consistent with the well-established safety profile of the
medicine.
The full DELIVER Phase III trial results will be submitted for
presentation at a forthcoming medical meeting and regulatory
submissions will be made in the coming months.
Notes
HF
HF affects approximately 64 million people
worldwide2,
at least half of whom have a reduced EF6,
including approximately 15 million in the EU7,
six million in the US8,
and 13.7 million treated adults in China9.
There are several main categories of HF related to EF, 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%)1,4.
HF with EF above 40% represents about half of all HF cases, and is
highly prevalent in patients with hypertension, T2D, obesity,
metabolic syndrome or CKD4,5,10.
HF remains as fatal as some of the most common cancers in both men
(prostate and bladder cancers) and women (breast
cancer)11.
Chronic HF is the leading cause of hospitalisation for those over
the age of 65 and represents a significant clinical and economic
burden12.
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 for all
comorbidities, including diabetes and hypertension, with the
exception of concomitant use of a sodium-glucose cotransporter 2
[SGLT2] inhibitor)13. DELIVER
is the largest clinical trial to date in HF patients with EF above
40%, with 6,263 randomised patients13,14.
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 Kansas City Cardiomyopathy Questionnaire at eight
months, time to the occurrence of CV death and time to the
occurrence of death from any cause13.
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
pancreas15-17.
Damage to one of these organs can cause the other organs to fail,
contributing to leading causes of death worldwide, including T2D,
HF and CKD2,18-20.
In the US,
Farxiga is approved as an
adjunct to diet and exercise to improve glycaemic control in adults
with T2D and in T2D to reduce the risk of hHF or CV death when
added to standard of care based on the findings of
the DECLARE-TIMI
58 Phase III CV outcomes
trial17. 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. In the European Union, Forxiga is indicated as both monotherapy (when
metformin is appropriate) and as part of combination therapy for
the treatment of insufficiently controlled T2D, with the additional
benefits of weight loss and blood-pressure reduction, as an adjunct
to diet and exercise in adults with T2D. Forxiga is also approved for
the treatment of symptomatic chronic HFrEF in adults with and without T2D and for
the treatment of
CKD in adults with and
without T2D.
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 the DAPA-MI Phase III trial - a first of
its kind, indication-seeking registry-based randomised controlled
trial in patients without T2D following an acute myocardial
infarction (MI) or heart attack21.
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. Cleveland Clinic
[Internet]. Heart failure; [cited 2022 Jan 11] Available
from: https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure
2. 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.
3. Mozaffarian D, et al. Heart disease
and stroke statistics-2016 update. Circulation. 2016; 133(4):e38-360.
4. Dunlay SM, et al. Epidemiology of
heart failure with preserved ejection
fraction. Nat Rev
Cardiol 2017;14(10):591-602.
5. 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.
6. Travessa AMR, et al. Treatment
of heart failure with reduced ejection fraction-recent
developments. Am J Ther 2016; 23(2):e531-49.
7. Dickstein K, et al. ESC
Guidelines for the diagnosis and treatment of acute and chronic
heart failure 2008: the Task Force for the Diagnosis and Treatment
of Acute and Chronic Heart Failure 2008 of the European Society of
Cardiology. Developed in collaboration with the Heart Failure
Association of the ESC (HFA) and endorsed by the European Society
of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29:2388-42.
8. Virani SS, et al. Heart
disease and stroke statistics-2020 update: a report from the
American Heart Association. Circulation 2020; 141(9):e139-e596.
9. AstraZeneca.
Data on File. February 2020.
10. Triposkiadis F, et al. Reframing the
association and significance of co-morbidities in heart
failure. Eur J Heart
Fail 2016;18(7):744-58.
11. Mamas MA, et al. Do patients have worse
outcomes in heart failure than in cancer? A primary care-based
cohort study with 10-year follow-up in
Scotland. Eur J Heart
Fail 2017;
19(9):1095-104.
12. Azad N, et al. Management of chronic
heart failure in the older population. J Geriatr
Cardiol. 2014;
11(4):329-37.
13. 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.
14. Clinicaltrials.gov
[Internet]. Dapagliflozin Evaluation to Improve the LIVEs of
Patients With Preserved Ejection Fraction Heart Failure; [cited
2022 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT03619213.
15. McMurray JJV, et al. Dapagliflozin
in patients with heart failure and reduced ejection
fraction. N Engl J
Med 2019;
381(21):1995-2008.
16. Heerspink HJL, et al. Dapagliflozin
in patients with chronic kidney disease. N Engl J
Med 2020;
383(15):1436-46.
17. 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.
18. Mayo Clinic
[Internet]. Heart failure, 2020; [cited 2022 Jan 11]. Available
from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
19. Centers for Disease Control and
Prevention (CDC) [Internet]. A snapshot: Diabetes in the United
States, 2020; [cited 2022 Jan 11]. Available
from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.
20. National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet].
Heart disease & kidney disease, 2016; [cited 2022 Jan 11].
Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease.
21. Clinicaltrials.gov
[Internet]. Dapagliflozin Effects on Cardiovascular Events in
Patients With an Acute Heart Attack (DAPA-MI); [cited 2022 Mar 10].
Available from: https://clinicaltrials.gov/ct2/show/NCT04564742.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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:
05 May 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|