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 November 2019
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Roxadustat
Phase III programme pooled analyses showed positive efficacy and no
increased cardiovascular risk in patients with anaemia from chronic
kidney disease
11 November 2019 07:00 GMT
Roxadustat Phase III programme pooled analyses showed
positive efficacy and no increased cardiovascular risk
in
patients with anaemia from chronic kidney disease
In non dialysis-dependent patients receiving roxadustat, the risk
of
MACE, MACE+ and all-cause mortality was comparable to
placebo
Dialysis-dependent patients receiving roxadustat had a lower risk
of MACE+
and no increased risk of MACE or all-cause mortality versus epoetin
alfa
In incident dialysis patients, roxadustat had a lower risk of MACE
and MACE+ and showed a trend towards lower risk of all-cause
mortality relative to epoetin alfa
AstraZeneca and FibroGen Inc. (FibroGen) have presented pooled
efficacy and cardiovascular (CV) safety analyses from the pivotal
Phase III programme assessing roxadustat for the treatment of
patients with anaemia from chronic kidney disease
(CKD).
The pooled CV safety analyses showed that roxadustat, an oral
first-in-class hypoxia-inducible factor prolyl hydroxylase
inhibitor (HIF-PHI), did not increase the risk of MACE, MACE+ and
all-cause mortality in non dialysis-dependent (NDD) patients
compared to placebo and dialysis-dependent (DD)
patients compared to epoetin alfa, a current medicine used to
treat anaemia.
In a clinically important predefined subgroup of incident dialysis
(ID) patients, defined as patients who have been on dialysis for
four months or less, roxadustat reduced the risk of MACE and MACE+
and showed a trend towards lower risk of all-cause mortality
relative to epoetin alfa.
Key safety endpoints consisted of time to major adverse CV events
(MACE), defined as all-cause mortality, stroke and myocardial
infarction, and time to MACE+, defined as MACE, unstable angina
requiring hospitalisation and congestive heart failure requiring
hospitalisation.
The results were presented in an oral late-breaking abstract
session at the American Society of Nephrology (ASN) Kidney Week
2019 in Washington, D.C., US.
Mene Pangalos, Executive Vice President, BioPharmaceuticals,
R&D, said: "These highly anticipated results reinforce our
confidence in the potential of roxadustat to address significant
unmet medical needs among patients with anaemia from chronic kidney
disease, particularly for those who have recently started dialysis.
The pooled analyses showed incident dialysis patients receiving
roxadustat had a lower risk of cardiovascular events which is
important as these patients may experience higher rates of
morbidity and mortality than those on stable
dialysis."
Robert Provenzano, MD, Associate Professor of Medicine, Wayne State
University, Detroit, Michigan, US and a primary investigator on the
global Phase III programme, said: "Roxadustat is the first in a new
class of medicines for the treatment of anaemia from chronic kidney
disease. This pooled cardiovascular safety data, together with
strong efficacy data, support its potential as an important new
treatment option for patients with anaemia from chronic kidney
disease who have seen little to no innovation in
decades."
Key headline data from the roxadustat Phase III programme pooled
safety analyses
|
Population
Comparator
|
MACE
|
MACE+
|
All-cause mortality
|
Conclusion
|
|
NDD
(n=4,270)
Placebo
|
HR
1.08
(95%
CI, 0.94, 1.24)
|
HR
1.04
(95%
CI, 0.91, 1.18)
|
HR
1.06
(95%
CI, 0.91, 1.23)
|
The
risk of MACE, MACE+ and all-cause mortality in roxadustat patients
was comparable to placebo
|
|
IDi,ii
(n=1,526)
Epoetin
alfa
|
HR
0.70
(95%
CI, 0.51, 0.96)
|
HR
0.66
(95%
CI, 0.50, 0.89)
|
HR
0.76
(95%
CI, 0.52, 1.11)
|
In ID
patients, those taking roxadustat had a 30% lower risk of MACE and
34% lower risk of MACE+ compared to those taking epoetin alfa, with
a trend towards lower all-cause mortality for roxadustat relative
to epoetin alfa
|
|
DD
(n=3,880)
Epoetin
alfa
|
HR
0.96
(95%
CI, 0.82, 1.13)
|
HR
0.86
(95%
CI, 0.74, 0.98)
|
HR
0.96
(95%
CI, 0.79, 1.17)
|
No
increased risk of MACE and all-cause mortality and a lower risk of
MACE+ compared to epoetin alfa
|
i.
ID patients are those who initiated dialysis within four months
prior to randomisation
ii.
ID patients are a subgroup of the DD patient
population
The primary efficacy endpoint was achieved in the pooled analyses
for NDD and DD patients, and in all individual Phase III trials.
Data from the pooled efficacy and CV safety analyses, together with
other statistical analyses, will form part of the regulatory
submission in the US, which is anticipated in Q4 2019.
The pooled efficacy analyses in the NDD population showed
roxadustat was superior to placebo, regardless of iron-repletion,
with a mean increase from baseline in haemoglobin (Hb) levels
averaged over weeks 28 to 52 of 1.85 g/dL in patients treated with
roxadustat compared to 0.13 g/dL with placebo
(p<0.001).
The pooled efficacy analyses in the DD population showed roxadustat
demonstrated a statistically significant mean increase from
baseline in Hb levels averaged over weeks 28 to 52 with 1.22 g/dL
in patients treated with roxadustat compared to 0.99 g/dL with
epoetin alfa (p<0.001).
Roxadustat is currently approved in China for the treatment of
anaemia in patients with CKD, regardless of whether they require
dialysis, and in Japan for the treatment of dialysis patients with
anaemia from CKD.
About roxadustat
Roxadustat is a HIF-PHI that promotes erythropoiesis by increasing
endogenous production of erythropoietin and improving iron
regulation and overcoming the negative impact of inflammation on
haemoglobin synthesis and red blood cell production by
downregulating hepcidin. Use of roxadustat has been shown to induce
coordinated erythropoiesis, increasing red blood cell count while
maintaining plasma erythropoietin levels within or near normal
physiologic range, in multiple subpopulations of CKD patients,
including in the presence of inflammation and without a need for
supplemental IV iron.
About the Phase III programme
FibroGen, Inc., (FibroGen) and AstraZeneca are collaborating on the
development and commercialisation of roxadustat for the treatment
of anaemia in patients with CKD in the US, China, and other global
markets. FibroGen and Astellas Pharma Inc. (Astellas) are
collaborating on the development and commercialisation of
roxadustat for the treatment of anaemia in patients with chronic
kidney disease (CKD) in territories including Japan, Europe, the
Commonwealth of Independent States, the Middle East, and South
Africa.
The global Phase III programme includes more than 9,000 patients
and was conducted by AstraZeneca, FibroGen and Astellas together.
The OLYMPUS, ALPS and ANDES trials evaluated roxadustat vs. placebo
in NDD patients. ROCKIES, SIERRAS and HIMALAYAS evaluated
roxadustat vs. epoetin alfa in DD patients. HIMALAYAS evaluated
roxadustat vs. epoetin alfa in ID patients; there were ID patients
in ROCKIES and SIERRAS. PYRENEES was not included in the pooled CV
safety analyses.
About anaemia
Anaemia can be a serious medical condition in which patients have
insufficient red blood cells and low levels of haemoglobin, a
protein in red blood cells that carries oxygen to cells throughout
the body.1,2 Anaemia
from CKD is associated with increased risk of hospitalisation, CV
complications and death,3 also
frequently causing significant fatigue, cognitive dysfunction and
decreased quality of life.4 Severe
anaemia is common in patients with CKD, cancer, myelodysplastic
syndrome, inflammatory diseases and other serious
illnesses.
Anaemia is particularly prevalent in patients with CKD. CKD affects
more than 200 million patients worldwide and is generally a
progressive disease characterised by gradual loss of kidney
function that may eventually lead to kidney failure.
According to the United States Renal Data System, about 80% of the
approximately 509,000 patients receiving dialysis in the US in 2016
were being treated with erythropoiesis-stimulating agents
(ESA).5 Patients
seldom receive ESA treatment until they initiate dialysis
therapy.
About AstraZeneca in CVRM
Cardiovascular, Renal & 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.
About AstraZeneca
AstraZeneca 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, CVRM, and Respiratory. AstraZeneca
operates in over 100 countries, and its innovative medicines are
used by millions of patients worldwide. For more information,
please visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
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References
1.
National Kidney Foundation. "Managing Anaemia When You Have Kidney
Disease or Kidney Failure." 2014.
2.
National Institute of Diabetes and Digestive and Kidney Diseases.
"Anaemia in Chronic Kidney Disease." 2014.
3.
Babitt JL, Lin HY. Mechanisms of Anemia in CKD. J Am Soc Nephrol
(2012); 23:1631-1634.
4.
KDOQI Clinical Practice Guidelines and Clinical Practice
Recommendations for Anaemia in Chronic Kidney
Disease. Am J Kidney
Dis. 2006 May; 47(5): S1-S132.
5. United States Renal
Data System. "Annual Data Report." 2017.
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:
11 November
2019
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|
By: /s/
Adrian Kemp
|
|
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Name:
Adrian Kemp
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|
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Title:
Company Secretary
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