Roxadustat Demonstrates Cardiovascular Safety in Global Phase III Clinical Trials

ShanghaiMay 16, 2019 /PRNewswire/ -- Today, AstraZeneca announced the results of a pooled analysis of cardiovascular (CV) safety from its global Phase III clinical studies on roxadustat. Roxadustat is the world’s first hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). This trial evaluated the efficacy and safety of roxadustat in treating anemia among patients with chronic kidney disease (CKD), including those who were non-dialysis-dependent (NDD), incident dialysis-dependent (ID), and maintenance dialysis-dependent.

The pooled analysis of cardiovascular safety is part of the overall benefit-risk assessment of roxadustat, and the relevant data will be used for pre-registration communications with regulatory authorities. One of the key endpoints for cardiovascular safety assessment in this trial was major adverse cardiovascular events (defined as MACE). A pooled analysis was conducted on the composite outcome of all-cause mortality, stroke, and myocardial infarction by comparing roxadustat with placebo in non-dialysis-dependent patients and roxadustat with alfaepoetin in dialysis-dependent patients. Another key safety endpoint was defined as MACE plus heart failure requiring hospitalization and unstable angina requiring hospitalization (defined as MACE+).

Non-dialysis (NDD) Patient'sMACEandMACE+Results

In a pooled analysis of more than 4,300 non-dialysis patients, based on all adjudicated evidence, the analyses of MACE and MACE+ did not show clinically meaningful differences between roxadustat and placebo.

Initial Unstable Dialysis (ID) Patient'sMACEandMACE+Results

In a pooled analysis of 1,500 initially unstable dialysis patients, the results for MACE and MACE+ demonstrated that roxadustat exhibited a better safety profile than epoetin alfa in the treatment of anemia among initially unstable dialysis patients. Given the relative stability of dialysis therapy and erythropoietin use in stable dialysis patients, this trial predefined the 1,500 initially unstable dialysis patients as a subgroup within the broader dialysis population to better illustrate the comparative outcomes between roxadustat and epoetin alfa.

Dialysis(DD)Patient'sMACEandMACE+Results

In a pooled analysis of approximately 4,000 dialysis patients, based on all adjudicated evidence, the results of MACE and MACE+ analyses did not show clinically meaningful differences between roxadustat and epoetin alfa.

Mene Pangalos, Executive Vice President of AstraZeneca and Head of BioPharmaceuticals R&D, stated, “Roxadustat is an innovative drug with a novel mechanism of action. We are delighted to share the results from the largest global clinical research program conducted for this drug to date. This marks another positive outcome in the study of roxadustat for the treatment of renal anemia, following the achievement of primary efficacy endpoints in the OLYMPUS and ROCKIES trials in December 2018. Currently, there remains a significant unmet medical need among patients with chronic kidney disease worldwide. We look forward to continuing our collaboration with FibroGen to advance the regulatory submission processes for roxadustat.”

Currently, the overall safety analysis of roxadustat is ongoing, and its benefit-risk assessment report will continue to be updated.

AstraZeneca and FibroGen will initiate relevant communications with the U.S. Food and Drug Administration (FDA) to prepare for the drug’s registration, with an application expected to be submitted in the second half of 2019. Currently, the China National Medical Products Administration has approved roxadustat for the treatment of anemia in patients with chronic kidney disease undergoing dialysis.