AstraZeneca 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 ...
(All Rights Reserved)