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 December 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.
Forxiga CHMP opinion for symptomatic chronic HF
19
December 2022 7:00 GMT
Forxiga recommended
for approval in the EU by CHMP
for symptomatic chronic heart failure
If approved, Forxiga will be the first heart failure therapy
indicated across the full ejection fraction range with proven
mortality reduction
AstraZeneca's Forxiga (dapagliflozin) has been recommended for
approval in the European Union (EU) to extend the indication for
heart failure with reduced ejection fraction (HFrEF) to cover
patients across the full spectrum of left ventricular ejection
fraction (LVEF) including HF with mildly reduced and preserved
ejection fraction (HFmrEF, HFpEF).
The Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency based its positive opinion
on results from the DELIVER Phase III trial, published
in The
New England Journal of Medicine1 and results from a pre-specified, patient
level, pooled analysis of the DAPA-HF and DELIVER Phase III trials
published in Nature
Medicine2. The pooled analysis
showed Forxiga to be the first HF medication to demonstrate
mortality benefit across the full ejection fraction
range3.
HF is a life-threatening chronic disease in which
the heart cannot pump enough blood around the
body4,
affecting 15 million people in the EU5.
Patients with HFmrEF or HFpEF experience an especially high burden
of symptoms and physical limitations, and a poor quality of life,
which is why improving health status is a key goal of
management6.
Mene Pangalos, Executive Vice President,
BioPharmaceuticals R&D, AstraZeneca, said: "Forxiga has already transformed the standard of care
for millions of people in the EU living with heart
failure. If approved for this
new, broader indication for heart failure with mildly reduced or
preserved ejection fraction, more patients will be able to benefit
from this well-tolerated and guideline-directed
treatment. As a leader in
cardiorenal disease, AstraZeneca is committed to expanding heart
failure treatment options, changing the way we treat this complex
disease to improve patient outcomes."
The CHMP recommendation
states Forxiga is indicated in adults for the treatment of
symptomatic chronic HF.
Results from the DELIVER Phase III trial in
patients with HFpEF and HFmrEF showed that Forxiga reduced the composite outcome of
cardiovascular (CV) death or worsening of HF by 18% (16.4% in the
dapagliflozin group and 19.5% in the placebo group [p<0.001,
absolute risk reduction [ARR] 3.1%] over a median follow-up of 2.3
years)1.
The treatment effect was consistent across the LVEF range, without
evidence of attenuation of effect by LVEF1.
Additionally, the pre-specified, patient level, pooled
analysis of the DELIVER and DAPA-HF Phase III trials
demonstrated that Forxiga reduced the risk of CV death by 14% (p=0.01,
ARR 1.5%), death from any cause by 10% (p=0.03, ARR 1.5%), and
total (first and repeat) hospitalisation for HF (hHF) by 29%
(p<0.001, ARR 6%) over the median follow-up of 22
months2.
Forxiga (known
as Farxiga in
the US) is approved for the treatment of patients with HFrEF in
more than 100 countries around the world including the US, the EU,
China and Japan. It was most recently approved in Great Britain and
Turkey to extend the HF indication to include patients across the
full spectrum of left ventricular ejection fraction. The HF
indication extension application is currently under review in the
US and other countries.
Notes
HF
HF is a chronic, long-term condition that worsens
over time7.
It affects nearly 64 million people globally8 and
is associated with substantial morbidity and
mortality9.
Chronic HF is the leading cause of hospitalisation for those over
the age of 65 and represents a significant clinical and economic
burden10.
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%)11.
Approximately half of all HF patients have HFmrEF or HFpEF, with
few therapeutic options available11,12.
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 Forxiga 10mg,
compared with placebo, given once daily in addition to standard of
care (SoC). 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. Key secondary endpoints included the
total number of 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)13.
DELIVER
DELIVER was an international, randomised,
double-blind, parallel-group, placebo-controlled, event-driven
Phase III trial designed to evaluate the efficacy
of Forxiga, compared with placebo, in the treatment of HF
patients with LVEF greater than 40%, with or without
T2D. Forxiga 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)14. DELIVER
is the largest clinical trial to date in HF patients with LVEF
above 40%, with 6,263 randomised patients14.
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
cause14.
Forxiga
Forxiga (dapagliflozin) is a first-in-class, oral,
once-daily SGLT2 inhibitor. Research has
shown Forxiga's efficacy in preventing and delaying
cardiorenal disease, while also protecting the organs - important
findings given the underlying links between the heart, kidneys and
pancreas13,15,16.
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) 4,8,17,18.
Forxiga is approved in adults and children aged 10
years and above for the treatment of insufficiently controlled T2D
mellitus as an adjunct to diet and
exercise. Forxiga is also approved for the treatment of HFrEF
in adults and the treatment of CKD in adults based on the findings
of the DAPA-HF and DAPA-CKD Phase III trials.
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;387:1089-1098.
2. 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.
2022;28:1956-1964.
3. AstraZeneca Press
Release [Internet]. New data show Farxiga significantly lowers the
risk of cardiovascular death in patients with heart failure [cited
2022 Nov 23]. Available from: https://www.astrazeneca.com/media-centre/press-releases/2022/farxiga-lowers-risk-cv-death-heart-failure.html.
4. Mayo Clinic
[Internet]. Heart failure [cited 2022 Nov 23]. Available
from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
5. 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; 29:2388-2442.
6. Warraich HJ, et al. Physical
function, frailty, cognition, depression, and quality of life in
hospitalized adults ≥60 years with acute decompensated heart
failure with preserved versus reduced ejection
fraction. Circ Heart
Fail.
2018;11:e005254.
7. Cleveland
Clinic [Internet]. Heart failure [cited 2022 Nov 23]. Available
from: https://my.clevelandclinic.org/health/diseases/17069-heart-failure-understanding-heart-failure.
8. 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.
9. Mozaffarian D, et al. Heart
disease and stroke statistics-2016 update. Circulation. 2016;133(4):e38-360.
10. Azad N, et al. Management of
chronic heart failure in the older
population. J Geriatr
Cardiol.
2014;11(4):329-37.
11. 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.
12. Dunlay SM, et al. Epidemiology of
heart failure with preserved ejection
fraction. Nat Rev
Cardiol 2017;14(10):591-602.
13. McMurray JJV, et al.
Dapagliflozin in patients with heart failure and reduced ejection
fraction. N
Engl J Med. 2019;381(21):1995-2008.
14. 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.
15. Heerspink HJL, et al. Dapagliflozin
in patients with chronic kidney disease. N Engl J
Med. 2020;383(15):1436-46.
16. 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.
17. Centers for
Disease Control and Prevention (CDC) [Internet]. A snapshot:
Diabetes in the United States [cited 2022 Nov 23]. Available
from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.
18. National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet].
Heart disease & kidney disease [cited 2022 Nov 23]. Available
from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease.
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:
19 December 2022
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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