TIDMAZN
RNS Number : 6303Y
AstraZeneca PLC
10 May 2019
This announcement contains inside information
10 May 2019 07:00 BST
Pooled analyses of the roxadustat global Phase III
programme confirmed cardiovascular safety
Cardiovascular safety endpoints evaluated across CKD
patients
not on dialysis, on incident dialysis and on stable dialysis
Better outcome vs. epoetin alfa in incident-dialysis
patients
and comparable to placebo in patients not on dialysis
AstraZeneca today announced top-line results from the pooled
cardiovascular (CV) safety analyses of the global Phase III
programme for roxadustat, a first-in-class hypoxia-inducible-factor
prolyl hydroxylase inhibitor (HIF-PHI). The global pivotal Phase
III trials evaluated roxadustat for treatment of anaemia in
patients with chronic kidney disease (CKD) across the
non-dialysis-dependent (NDD), incident (newly-initiated) dialysis
(ID), and stable dialysis patient groups.
These pooled CV safety assessments of roxadustat are part of the
overall benefit/risk assessment that will inform discussions with
regulatory authorities. One of the key CV safety endpoints is major
adverse CV events (defined as MACE), evaluating a composite of
all-cause mortality, stroke and myocardial infarction in pooled
analyses comparing roxadustat vs. placebo in NDD and vs. epoetin
alfa in dialysis-dependent (DD) patients. Another key CV safety
endpoint evaluated MACE plus heart failure requiring
hospitalisation and unstable angina requiring hospitalisation
(defined as MACE+).
Pooled MACE/MACE+ in NDD patients
In the pooled analysis of over 4,300 patients, and based on the
totality of the adjudicated evidence, the MACE/MACE+ analyses
between roxadustat and placebo showed no clinically-meaningful
difference.
Pooled MACE/MACE+ in ID patients
In the pool of 1,500 ID patients, a pre-specified sub-population
of DD patients, MACE/MACE+ results indicate that ID patients on
roxadustat do better than those who are on epoetin alfa. ID
patients are a better population to compare roxadustat vs. epoetin
alfa than the stable dialysis population, where patients are stable
not only on dialysis but also on erythropoietin.
Pooled MACE/MACE+ in DD patients
In the pooled analysis of around 4,000 patients, and based on
the totality of the adjudicated evidence, the MACE/MACE+ analyses
between roxadustat and epoetin alfa showed no clinically-meaningful
difference.
Mene Pangalos, Executive Vice President, R&D
BioPharmaceuticals, said: "We are pleased to report these data from
the largest clinical programme in the world evaluating this new
class of medicines. These results add to the growing body of
positive evidence to support roxadustat for the treatment of
anaemia in chronic kidney disease patients, following our
announcement that the primary efficacy endpoints were met for the
OLYMPUS and ROCKIES trials in December 2018. There is a significant
unmet medical need among patients living with chronic kidney
disease, and we look forward to working with FibroGen to prepare
for regulatory submissions of roxadustat."
Further analyses of overall safety are ongoing and will inform
the benefit/risk profile.
AstraZeneca and FibroGen Inc. (FibroGen) will begin discussions
with the US Food and Drug Administration (FDA) to prepare for
regulatory submission, which is anticipated in the second half of
2019. Roxadustat is currently approved in China for the treatment
of patients with anaemia in DD 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 intravenous iron.
About the global Phase III clinical programme
FibroGen, the originator, 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 CKD in
territories including Japan, Europe, the Commonwealth of
Independent States, the Middle East, and South Africa.
The global Phase III programme consists of more than 9,000
patients and was conducted by AstraZeneca, FibroGen and
Astellas.
The OLYMPUS, ALPS and ANDES trials evaluated roxadustat vs.
placebo in NDD patients; HIMALAYAS evaluated roxadustat vs. epoetin
alfa in ID patients; and ROCKIES, SIERRAS and PYRENEES evaluated
roxadustat vs. epoetin alfa in DD patients.
The AstraZeneca-sponsored trial OLYMPUS demonstrated a
statistically-significant and clinically-meaningful improvement in
haemoglobin vs. placebo in NDD patients. The AstraZeneca-sponsored
trial ROCKIES demonstrated a statistically-significant improvement
in haemoglobin vs. epoetin alfa in DD patients.
In the CV pooled safety analyses, safety was characterised based
on a number of key CV analyses from the Phase III programme,
including MACE outcomes and MACE+ outcomes (MACE plus
hospitalisation for unstable angina and hospitalisation for heart
failure outcomes). Overall, the analyses will evaluate the totality
of evidence for roxadustat and assess the overall benefit-risk
profile, to overcome potential bias of a single-arm trial
analysis.
About anaemia in CKD
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 in 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, which
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.
In the US, according to the United States Renal Data System, a
majority of dialysis-eligible CKD patients are currently on
dialysis. Of the approximately 507,000 patients receiving dialysis
in the US as of 2016, approximately 80% were being treated with
erythropoiesis-stimulating agents (ESA) for anaemia.(5) Patients
seldom receive ESA treatment until they initiate dialysis
therapy.
About AstraZeneca in CV, Renal & Metabolism (CVRM)
CV, renal and metabolism together form one of AstraZeneca's main
therapy areas and 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. Our 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.
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, 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
astrazeneca.com and follow us 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.
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