WASHINGTON—Roxadustat is superior to epoetin alfa in raising hemoglobin (Hb) levels in incident dialysis patients with anemia, according the results of the phase 3 HIMALAYAS trial of roxadustat presented at the American Society of Nephrology’s Kidney Week 2019 meeting.
In the trial, investigators randomly assigned 1043 patients in 17 countries (who initiated dialysis within 4 months of randomization) to roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), or epoetin alfa, an erythropoiesis-stimulating agent (ESA). At baseline, mean Hb was 8.43 vs 8.46 g/dL for roxadustat and epoetin patients, respectively. A third of patients in each arm had type 2 diabetes. Fewer than 10% of patients in each arm were black.
Over weeks 28 to 52, mean Hb increased significantly more with roxadustat: 2.57 vs 2.36 g/dL, respectively, lead investigator Robert Provenzano, MD, of CMO Nephrology Practice Solutions, DaVita Healthcare, in Denver, reported in an oral presentation. Criteria for non-inferiority and superiority were met. Hb response rate was likewise higher with roxadustat: 88.2% vs 84.4%, respectively.
In addition to increasing endogenous production of erythropoietin, roxadustat improves iron regulation and eases the negative impact of inflammation on hemoglobin synthesis and red blood cell production by downregulating hepcidin. Roxadustat was noninferior to epoetin alfa among patients who were iron deplete and/or inflamed at baseline.
Roxadustat recipients also required less intravenous iron than epoetin patients to achieve similar levels of iron repletion.
“Roxadustat is the first of a new class of medication, applying the groundbreaking science on oxygen sensing and adaptation to hypoxia recently awarded the 2019 Nobel Prize in Physiology or Medicine,” Dr Provenzano, Associate Professor of Medicine at Wayne State University in Detroit, stated in a news release. “The positive HIMALAYAS results highlight the potential of roxadustat as an attractive new treatment option for anemia in these highly vulnerable patients who are new to dialysis care. This study provides useful insights and clinically relevant data for consideration in clinical practice, as most patients start anemia treatment when they begin dialysis.”
Roxadustat was administered thrice weekly with the initial dose based on weight. Epoetin was administered per the product label in each country. Patients were previously naïve to ESAs or had limited prior use. During the trial, oral iron was allowed but parenteral iron was not.
The most frequently observed adverse events with roxadustat in the HIMALAYAS trial were hypertension, diarrhea, and muscle spasms.
Pooled safety findings from all 3 of the major roxadustat trials were also reported at Kidney Week as a late-breaking oral abstract session. In incident dialysis patients, roxadustat was associated with a 30% lower risk of major adverse cardiovascular events (MACE), defined as all-cause mortality, stroke and myocardial infarction, and a 34% lower risk of MACE+, defined as MACE, unstable angina requiring hospitalization and congestive heart failure requiring hospitalization, with a trend towards lower all-cause mortality compared with epoetin alfa.
The HIMALAYAS study was funded by FibroGen, Inc. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the treatment of CKD anemia in the United States.
Provenzano R, Besarab A, Leong R, et al. HIMALAYAS: A Phase 3, Randomized, Open-Label, Active-Controlled Study of the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Incident-Dialysis Patients. Presented at: Kidney Week 2019. November 5-10, 2019. Washington DC. Oral abstract TH-OR021.
Pooled Efficacy and CV Safety of Roxadustat vs Placebo in NDD-CKD Patients and Epoetin Alfa in DD-CKD patients. Presented at: Kidney Week 2019. November 5-10, 2019. Washington DC. Late-breaking oral abstract. FR-OR131.
FibroGen Presents Phase 3 Efficacy and Safety Results for Roxadustat Versus Epoetin Alfa as Treatment of Anemia in Incident Dialysis Patients with Chronic Kidney Disease [news release]. November 7, 2019.
Roxadustat Phase III Program Pooled Analyses Showed Positive Efficacy and No Increased Cardiovascular Risk in Patients with Anemia from Chronic Kidney Disease Versus Comparators [news release]. AstraZeneca; November 8, 2019.