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) today presented pooled
efficacy and cardiovascular (CV) safety analyses from the pivotal
Phase III program assessing roxadustat for the treatment of
patients with anemia from chronic kidney disease (CKD).
The pooled CV safety analyses showed that roxadustat, an oral
investigational 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) compared to
placebo and dialysis-dependent (DD) patients compared to epoetin
alfa, a current medicine used to treat anemia.
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 hospitalization and congestive heart failure
requiring hospitalization.
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.
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 anemia 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 program, said: “In the US, roxadustat has
the potential to be the first in a new class of medicines for the
treatment of anemia 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 anemia from chronic kidney disease who have seen
little to no innovation in decades.”
Key headline data from the roxadustat Phase III program
pooled CV 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
- ID patients are those who initiated dialysis within four months
prior to randomization
- 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 demonstrated a statistically significant mean increase
from baseline in hemoglobin (Hb) levels, regardless of iron
repletion, 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).
About roxadustat
Roxadustat is an investigational hypoxia-inducible factor prolyl
hydroxylase inhibitor (HIF-PHI) that has the potential to promote
erythropoiesis by increasing endogenous production of
erythropoietin and improving iron regulation and overcoming the
negative impact of inflammation on hemoglobin synthesis and red
blood cell production resulting in a downregulation of hepcidin.
Use of roxadustat may 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.
About the Phase III program
FibroGen, Inc., (FibroGen) and AstraZeneca are collaborating on
the development and commercialization of roxadustat for the
treatment of anemia in patients with CKD in the US, China, and
other global markets. FibroGen and Astellas Pharma Inc. (Astellas)
are collaborating on the development and commercialization of
roxadustat for the treatment of anemia 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 program 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 anemia
Anemia can be a serious medical condition in which patients have
insufficient red blood cells and low levels of hemoglobin, a
protein in red blood cells that carries oxygen to cells throughout
the body. Anemia from CKD is associated with increased risk of
hospitalization, CV complications and death, also frequently
causing significant fatigue, cognitive dysfunction and decreased
quality of life. Severe anemia is common in patients with CKD,
cancer, myelodysplastic syndrome, inflammatory diseases and other
serious illnesses.
Anemia is particularly prevalent in patients with CKD. CKD
affects more than 200 million patients worldwide and is generally a
progressive disease characterized 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 507,000 patients receiving dialysis in the US in
2016 were being treated with erythropoiesis-stimulating agents
(ESA). 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 commercialization of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal &
Metabolism and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. For more information, please visit
www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
US- 32753 Last Updated 11/19
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191108005530/en/
Media Inquiries Michele Meixell +1 302 885 2677
AstraZeneca (NYSE:AZN)
Historical Stock Chart
Von Feb 2024 bis Mär 2024
AstraZeneca (NYSE:AZN)
Historical Stock Chart
Von Mär 2023 bis Mär 2024