HIMALAYAS trial shows roxadustat superior to epoetin alfa in raising hemoglobin levels
WASHINGTON — Compared to epoetin alfa, roxadustat was more effective in raising hemoglobin levels and used less iron therapy in incident patients with kidney disease on dialysis, according to results from U.S. and European studies presented here.
Phase 3 of the HIMALAYAS trial tested roxadustat in incident patients with ESKD on dialysis who were matched 1:1 with patients using epoetin alfa (EPO). Patients in both groups had similar hemoglobin levels and the dialysis modality was similar.
“These were severely anemic patients,” Robert Provenzano, MD, chief investigator on the trial, said. “Thirty percent had a hemoglobin less than 8 (g/dL).” Patients in the EPO group had fewer than 3 months of exposure to the drug.
Provenzano said there was a growing need to address anemia in patients transitioning from chronic kidney disease to dialysis.
“We know that mortality is high ... and they get into a system where they are disadvantaged. We don’t treat these transition patients with erythropoietin. They start [dialysis] with nothing,” Provenzano said.
Roxadustat was given in pill form and dosed thrice weekly; initial dosing was weight based, while EPO was prescribed according to the country-specific product labeling. Study protocols allowed the use of oral iron; parenteral iron was restricted.
The primary endpoint for the U.S. trial was to assess the mean hemoglobin change from baseline during weeks 28 to 52; the primary endpoint for the European trial was to identify the percentage of patients achieving a hemoglobin response through weeks 1 to 24.
The investigators determined a hemoglobin response was two consecutive visits during the first 24 weeks of the trial where a hemoglobin level of 11 g/dL was achieved, as well as an increase of 1 g/dL if the baseline hemoglobin was less than 8 g/dL or an increase of 2 g/dL if the baseline hemoglobin was less than 8 g/dL.
In the study, 1,043 patients (522= roxadustat; 521 = EPO) were randomized in 17 countries and matched for comorbidities. Mean hemoglobin change from baseline was 2.57 g/dL in the roxadustat group compared to 2.36 g/dL in the patient group using EPO.
“The overall safety profile was consistent with results observed in prior [roxadustat] ROXA trials ... ,” the researchers said. “ROXA was noninferior and subsequently demonstrated superiority over EPO in the mean change in [hemoglobin] from [baseline] in patients incident to dialysis.” – by Mark E. Neumann
Provenzano R, et al. Abstract TH-OR021. 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.