WASHINGTON — Roxadustat showed efficacy with no increased cardiovascular risk for patients with anemia from chronic kidney disease, according to pooled efficacy data presented here at ASN Kidney Week.
“These are unique populations. The study pooled all of our knowledge in treating anemia in each of them,” Robert Provenzano, MD, of DaVita Healthcare, said.
Provenzano and colleagues pooled phase 3 randomized studies that compared roxadustat for patients with stages 3 to 5 nondialysis-dependent CKD to placebo and epoetin alfa in dialysis-dependent patients. Key safety endpoints were time to major adverse cardiovascular event (MACE), which was defined as all-cause mortality, stroke and myocardial infarction; and time to MACE+, defined as MACE, unstable angina that required hospitalization and congestive heart failure requiring hospitalization. They also assessed efficacy by hemoglobin and rescue therapy, which was blood transfusion, IV iron and erythropoiesis-stimulating agents.
For the pooled analyses of the 4,270 patients in the nondialysis-dependent dialysis group, 2,386 patients received roxadustat and 1,884 patients had placebo. For the patients who received roxadustat, researchers found the risk of MACE, MACE+ and all-cause mortality was comparable to patients in the placebo group. The mean increase from baseline in hemoglobin levels averaged during weeks 28 to 52 was 1.85 g/dL in the roxadustat group compared with 0.13 g/dL in placebo group. Roxadustat patients had a lower risk of rescue therapy.
For the pooled analyses of the 3,917 dialysis-dependent patients, 1,960 patients received roxadustat and 1,957 patients had epoetin alfa. Patients who received roxadustat had a lower risk of MACE+ and no increased risk of MACE or all-cause mortality compared with patients in the epoetin alfa group. The mean increase from baseline in hemoglobin levels average over weeks 28 to 52 was 1.22 g/dL for patients who received roxadustat vs. 0.99 g/dL for patients in the epoetin alfa group and this difference was statistically significant. Patients who received roxadustat had fewer transfusions.
Of the 1,526 incident dialysis patients, defined as patients who have been on dialysis for 4 months or less, roxadustat lowered the risk of MACE and MACE+ with a trend toward lower risk of all-cause mortality relative to epoetin alfa.
For patients with infectious diseases, those taking roxadustat had a 30% lower risk of MACE and 34% lower risk of MACE+ compared with patients who received epoetin alfa, with a trend toward lower all-cause mortality for roxadustat relative to epoetin alfa.
“Cardiovascular safety was demonstrated in all study populations,” Provenzano said.
Roxadustat is an oral first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor. – by Kristine Houck, MA, ELS
Provenzano R, et al. Abstract FR-OR131 Presented at: ASN Kidney Week; Nov. 7-10, 2019; Washington D.C.
Disclosure: Provenzano reports he is vice president for medical affairs for DaVita; is on the board of directors for Nephroceuticals and Vasc-Alert; and received study funding from FibroGen, AstraZeneca and Astella.