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 March
2020
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 Phase III DAPA-CKD
trial will be stopped early after
overwhelming efficacy in patients with chronic kidney
disease
30 March 2020 07:00 BST
Farxiga Phase III DAPA-CKD trial will be stopped
early after
overwhelming efficacy in patients with chronic kidney
disease
Farxiga is the first SGLT2 inhibitor to show meaningful benefit in
patients with chronic kidney disease in a trial including both
type-2 diabetics and non-diabetics
The Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) Phase III trial
for Farxiga (dapagliflozin) in patients with chronic
kidney disease (CKD) will be stopped early following a
recommendation from an independent Data Monitoring Committee (DMC)
based on its determination of overwhelming
efficacy.
The decision to stop the trial early was made following a routine
assessment of efficacy and safety which
showed Farxiga's benefits earlier than originally anticipated
and AstraZeneca will now initiate closure of the
trial.
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "Chronic kidney disease patients have limited
treatment options, particularly those without type-2 diabetes. We
are very pleased the Data Monitoring Committee concluded that
patients experienced overwhelming benefit. Farxiga has the potential to change the management
of chronic kidney disease for patients around the
world."
The co-chairs of the trial and its Executive Committee Prof. David
Wheeler, University College London, and Prof. Hiddo L. Heerspink,
University Medical Center Groningen, said: "It has been a privilege
to be involved in this trial. We are delighted with the Data
Monitoring Committee recommendation and look forward to sharing the
results with the medical community and patients with chronic kidney
disease."
The primary endpoint of DAPA-CKD is a composite of worsening of
renal function or death (defined as a composite endpoint of
≥50% sustained decline in estimated glomerular
filtration rate (eGFR), onset of end-stage kidney disease (ESKD) or
cardiovascular (CV) or renal death) in patients with CKD
irrespective of the presence of type-2 diabetes
(T2D).1
The full results will be submitted for presentation at a
forthcoming medical meeting and AstraZeneca will now initiate
discussions with global health authorities regarding early
regulatory submissions.
In August
2019, the US Food and Drug
Administration (FDA) granted Fast Track designation for the
development of Farxiga to delay the progression of renal failure
and prevent CV and renal death in patients with
CKD. Farxiga is under Priority
Review with the FDA and
under regulatory review at the European Medicines Agency (EMA), as
well as in other regions, for the treatment of patients with heart
failure (HF).
Chronic kidney disease
CKD can be a serious, progressive condition defined by decreased
kidney function (shown by reduced eGFR or markers of kidney damage,
or both, for at least three months).2 The
most common causes of CKD are diabetes, hypertension and
glomerulonephritis.3 CKD
is associated with significant patient morbidity and an increased
risk of CV events,4 such
as HF and premature death.5 In
its most severe form, known as ESKD, kidney damage and
deterioration of kidney function have progressed to the stage where
dialysis or kidney transplantation are required.6 The
majority of patients with CKD will die from CV causes before
reaching ESKD.7
DAPA-CKD
DAPA-CKD is an international, multi-centre, randomised,
double-blinded trial in 4,245 patients designed to evaluate the
efficacy of Farxiga 10mg, compared with placebo, in patients
with CKD stages 2-4 and elevated urinary albumin excretion, with
and without T2D. Farxiga is given once daily in addition to standard
of care. The primary composite endpoint is worsening of renal
function (defined as a composite of an eGFR decline ≥50%,
onset of ESKD and death from CV or renal cause). The trial is being
conducted in 21 countries. The efficacy-stopping guideline in the
trial protocol and DMC Charter state that after evaluating the
totality of the available efficacy and safety data, the DMC may
consider recommending that the study be stopped for overwhelming
efficacy.
Farxiga
Farxiga (dapagliflozin) is
a first-in-class, oral, once-daily sodium-glucose co-transporter-2
(SGLT2) 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 CV outcomes trial in
adults with T2D, Farxiga reduced the risk of the composite endpoint
of hospitalisation for HF or CV death versus placebo, when added to
standard of care.
In the DAPA-HF trial, Farxiga on top of standard of care reduced both the
incidence of cardiovascular death and the worsening of heart
failure in patients with HF with reduced ejection fraction (HFrEF),
with and without T2D. Farxiga is also being tested for patients with HF in
the DELIVER (HF with preserved ejection fraction, HFpEF) and
DETERMINE (HFrEF and HFpEF) trials. Farxiga 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 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 cardiovascular health for millions of patients
worldwide.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: 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 and Metabolism, and Respiratory.
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. Hiddo
J L Heerspink et al. Rationale and protocol of the Dapagliflozin
And Prevention of Adverse outcomes in Chronic Kidney Disease
(DAPA-CKD) randomized controlled trial, Nephrology
Dialysis Transplantation,
Volume 35, Issue 2, February 2020, Pages
274-282, https://doi.org/10.1093/ndt/gfz290.
2. Mallappallil, M., Friedman, E. A.,
Delano, B. G., McFarlane, S. I., & Salifu, M. O. (2014).
Chronic kidney disease in the elderly: evaluation and
management. Clinical
practice (London,
England), 11(5), 525-535.
doi:10.2217/cpr.14.46.
3.
National Kidney Foundation. Kidney Disease: Causes, 2017; [cited
2020 Mar 28]. Available from URL:
https://www.kidney.org/atoz/content/kidneydiscauses.
4. Bikbov, Boris, et al. "Global,
Regional, and National Burden of Chronic Kidney Disease, 1990-2017:
a Systematic Analysis for the Global Burden of Disease Study
2017." The Lancet, vol. 395, no. 10225, 13 Feb. 2020, pp. 709-733.,
doi:10.1016/s0140-6736(20)30045-3.
5. Segall L et al. Heart failure in
patients with chronic kidney disease: A systematic integrative
review. Biomed Res
Int 2014;
2014:937398.
6. Centers for
Disease Control and Prevention. Chronic Kidney Disease in the
United States, 2019; [cited 2020 Mar 27]. Available from
URL: https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.html.
7. Thompson S, James M, Wiebe N,
Hemmelgarn B, Manns B, Klarenbach S and Tonelli M. Cause of Death
in Patients with Reduced Kidney Function. Journal of the American
Society of Nephrology. 2015, 26
(10) 2504-2511; DOI:
https://doi.org/10.1681/ASN.2014070714.
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:
30 March
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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