a4479c
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 October 2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
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United
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Forxiga HF receives positive CHMP opinion
19 October 2020 07:00 BST
Forxiga recommended for approval in the EU by CHMP
for heart failure
If approved, Forxiga would become the first SGLT2 inhibitor
indicated for heart failure with reduced ejection fraction in
patients with and without type-2 diabetes
AstraZeneca's Forxiga (dapagliflozin) has been recommended for an
indication extension of its marketing authorisation in the European
Union (EU) for the treatment of symptomatic chronic heart failure
with reduced ejection fraction (HFrEF) in adults with and without
type-2 diabetes (T2D). Heart failure (HF) is a life-threatening
chronic disease in which the heart cannot pump enough blood around
the body,1 affecting
15 million people in the EU, at least half of which have a reduced
ejection fraction.2,3
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) based its positive opinion on
results from the landmark DAPA-HF Phase III trial, published
in The
New England Journal of Medicine.4
Forxiga is the first SGLT2
inhibitor to have shown a statistically significant reduction in
the risk of cardiovascular (CV) death or worsening of HF events
(including hospitalisation for HF, hHF) versus placebo where both
components of the primary composite endpoint contributed benefit to
the overall effect. In the DAPA-HF Phase III trial, the safety
profile of Forxiga was consistent with the well-established
safety profile of the medicine.
John McMurray, MD, Cardiovascular Research Centre, Institute of
Cardiovascular and Medical Sciences, University of Glasgow, UK,
said: "I am delighted that we may soon have a new treatment that is
effective, safe and simple to use for patients with heart failure
with reduced ejection fraction. Dapagliflozin is a major and
welcome breakthrough with the potential to improve not only the
quality, but also importantly, the length of life for millions of
people suffering from this terrible disease in Europe and
throughout the world."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "The unmet need for novel medicines in heart failure
remains high, with more than half of patients expected to die
within five years of diagnosis. Novel treatment options
reducing cardiovascular death and hospitalisation, in addition to
improving symptoms, are urgently needed. With the positive
opinion for Forxiga we are one step closer to transforming the
standard of care for millions of people in the EU living with heart
failure."
The DAPA-HF Phase III trial demonstrated
that Forxiga, in addition to standard of care, reduced the
risk of the composite outcome of CV death or the worsening of HF
versus placebo by 26% (hazard ratio [HR] = 0.74 [95% confidence
interval {CI} 0.65-0.85]; p < 0.0001) (absolute risk
reduction [ARR] = 4.9% [16.3% vs 21.2% patients with event,
respectively]). During the trial, one CV death or hHF or an urgent
visit associated with HF could be avoided for every 21 patients
treated.
The CHMP recommendation states Forxiga is indicated in adults for the treatment of
symptomatic chronic HFrEF.
Forxiga (known
as Farxiga in the US) is approved by
the US Food and Drug Administration (FDA), as well as in several
other countries around the world, for the for the treatment of
patients with HFrEF.
Forxiga is evolving
cardiorenal prevention as science continues to identify the
underlying links between the heart, kidneys and
pancreas. DAPA-HF is part of DapaCare, a robust
clinical trial programme to assess the potential CV and renal
benefits of Forxiga, including the DECLARE-TIMI 58 trial which first
evaluated Forxiga for the treatment of hHF and CV risk factors
in patients with T2D. The programme has also explored the treatment
of patients with chronic kidney disease (CKD) in the
ground-breaking DAPA-CKD Phase III trial and is also currently
being tested for HF patients with preserved ejection fraction
(HFpEF) in the DELIVER Phase III trial with data anticipated in the
second half of 2021.
Heart failure
HF is a life-threatening disease in which the heart cannot pump
enough blood around the body.1 It
affects approximately 64 million people worldwide (at least half of
which have a reduced ejection fraction), including 15 million in
the EU and six million in the US.2-3,5 It
is a chronic disease where half of patients will die within five
years of diagnosis.6 There
are two main categories of HF related to ejection fraction (EF), a
measurement of the percentage of blood leaving the heart each time
it contracts: HFrEF and HFpEF.7 HFrEF
occurs when the left ventricle (LV) muscle is not able to contract
adequately and therefore, expels less oxygen-rich blood in to the
body.7,8 HF
remains as fatal as some of the most common cancers in both men
(prostate and bladder cancers) and women (breast
cancer).9 It
is the leading cause of hospitalisation for those over the age of
65 and represents a significant clinical and economic
burden.10
DAPA-HF
DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart
Failure) is an international, multi-centre, parallel-group,
randomised, double-blinded Phase III trial in 4,744 patients with
HFrEF (LVEF ≤ 40%), with and without T2D, designed to
evaluate the effect of Forxiga 10mg,
compared with placebo, given once daily in addition to standard of
care. 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.
Forxiga
Forxiga (dapagliflozin) is
a first-in-class, oral, once-daily sodium-glucose co-transporter-2
inhibitor indicated in adults for the treatment of insufficiently
controlled T2D as both monotherapy and as part of combination
therapy as an adjunct to diet and exercise to improve glycaemic
control, with the additional benefits of weight loss and
blood-pressure reduction. In the DECLARE-TIMI 58 CV outcomes trial
in adults with T2D, Forxiga reduced the risk of the composite endpoint
of hHF or CV death versus placebo, when added to standard of
care.
In May
2020, Farxiga was
approved in the US to reduce the risk of CV death and hHF in adults
with HF (NYHA class II-IV) with reduced ejection fraction with and
without T2D. Forxiga has
also been evaluated in patients with CKD in the DAPA-CKD Phase III
trial, with the full results announced in August
2020 showing Forxiga met
all primary and secondary endpoints, providing overwhelming
efficacy. Forxiga is currently being tested for patients with
HF in the DELIVER (HFpEF) and DETERMINE (HFrEF and HFpEF) Phase III
trials. Forxiga will also be tested in patients without T2D
following an acute myocardial infarction (MI) or heart attack in
the DAPA-MI Phase III trial - a first of its kind,
indication-seeking registry-based randomised controlled
trial. Forxiga has a robust programme of clinical trials
that 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.
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM) together forms one of
AstraZeneca's three therapy 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 to protect
organs and improve outcomes by slowing disease progression,
reducing risks and tackling comorbidities. 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 cardiovascular 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, primarily for the treatment of diseases in three therapy
areas - Oncology, 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.
Mayo Clinic. Heart failure; 2017 [cited 18 October 2020]. Available
from: URL:
https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
2. 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.
3. Travessa AMR, Menezes Falcão
LF de. Treatment of Heart Failure With Reduced Ejection
Fraction-Recent Developments. Am J Ther 2016; 23(2):e531-49.
4. McMurray JJV et al. Dapagliflozin
in Patients with Heart Failure and Reduced Ejection
Fraction. N Engl J
Med 2019.
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. The
Lancet 2017;
390(10100):1211-59.
6. Mozaffarian D et al. Heart Disease
and Stroke Statistics-2016 Update: A Report From the American Heart
Association. Circulation 2016; 133(4):e38-360.
7. Ponikowski P et al. 2016 ESC
Guidelines for the diagnosis and treatment of acute and chronic
heart failure: The Task Force for the diagnosis and treatment of
acute and chronic heart failure of the European Society of
Cardiology (ESC)Developed with the special contribution of the
Heart Failure Association (HFA) of the
ESC. Eur
Heart J 2016;
37(27):2129-200.
8.
National Institute for Health and Care Excellence. Chronic heart
failure in adults: diagnosis and management: NICE guideline
[NG106]; 2018 [cited 18 October 2020]. Available from: URL:
www.nice.org.uk/guidance/ng106.
9. 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.
10. Azad N, Lemay G. Management of chronic
heart failure in the older population. J Geriatr
Cardiol 2014;
11(4):329-37.
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 October 2020
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By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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