Roxadustat strides ahead as anaemia treatment in CKD

Roxadustat appears a promising treatment for anaemia in patients with chronic kidney disease (CKD), regardless of whether they are undergoing dialysis, according to two analyses presented at ASH 2020.

The first study was a pooled analysis of three open-label phase III trials which randomized 3,917 patients with CKD undergoing dialysis (1:1) to receive either roxadustat or epoetin alfa (EPO) for anaemia (mean age 54.3 and 55.1 years, respectively). Baseline haemoglobin (Hb) levels were comparable in the two arms (mean 9.63 and 9.67 g/dL, respectively), and 9.3 and 9.8 percent, respectively, received peritoneal dialysis, with the others receiving haemodialysis.

Between weeks 28 and 52, mean Hb change from baseline with roxadustat was noninferior and superior compared with EPO in each of the three trials, as well as in the pooled analysis (mean change 1.21 vs 0.95 g/dL; difference, 0.26 g/dL, 95 percent confidence interval [CI], 0.20–0.33; p<0.0001). [ASH 2020, abstract 749]

Patients on roxadustat were less likely to receive red blood cell (RBC) transfusions than those on EPO (9.5 percent vs 12.8 percent; hazard ratio [HR], 0.82).

Among all dialysis patients, major adverse cardiovascular event (MACE) incidence, comprising death, myocardial infarction, and stroke, was lower among roxadustat vs EPO recipients (HR, 0.96, 95 percent CI, 0.82–1.13). Heart failure or unstable angina warranting hospitalization (MACE+) was significantly less likely in roxadustat than EPO recipients (HR, 0.86, 95 percent CI, 0.74–0.98; p=0.028).

This risk was further reduced among the 1,526 patients with incident dialysis (≤4 months of dialysis; MACE: HR, 0.70; p=0.029; MACE+: HR, 0.66; p=0.005).

“Anaemia affects >90 percent of patients with CKD who require dialysis,” said study first author Professor Steven Fishbane from the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, US, and co-authors.

While erythropoiesis-stimulating agents (ESAs) with or without intravenous iron and RBC transfusions are standard of care treatment, ESAs have been associated with cardiovascular (CV) and mortality risk, particularly at higher doses which CKD patients often require. To counteract this risk, CKD patients with anaemia may receive suboptimal doses of ESA and more transfusions.

“[This analysis showed that] roxadustat was noninferior and superior in increasing Hb compared with EPO in three phase III trials. It also significantly reduced MACE risk in incident dialysis patients and MACE+ risk in … the all-dialysis … and incident dialysis patient groups. Additionally, roxadustat reduced RBC transfusion compared with EPO in the all-dialysis pooled analysis,” the authors said.

Benefits in non-dialysis population

In an analysis of three double-blind phase III trials, 4,270 patients with stage 3–5 CKD not on dialysis with a Hb level <10 g/dL (baseline Hb 9.1 g/dL) were randomized to receive roxadustat (n=2,386) or placebo (n=1,884). 

Mean Hb change from baseline with roxadustat was noninferior and superior to placebo between weeks 28 and 52 for each study (p<0.001) and in the pooled analysis (1.85 vs 0.13 g/dL; p<0.0001). [ASH 2020, abstract 1671]

There was an 81 percent reduction in the need for rescue therapy (transfusion, intravenous iron, ESAs) in the roxadustat vs placebo group up to week 52 (HR, 0.19, 95 percent CI, 0.16–0.23; p<0.0001), as well as a 74 percent reduction in RBC transfusion (HR, 0.26, 95 percent CI, 0.21–0.32; p<0.001).

Roxadustat recipients also demonstrated a reduction in LDL-cholesterol levels up to week 28 (p<0.0001). In the 2,456 patients with baseline eGFR ≥5 mL/min/1.73 m², there was a 1.6 mL/min/1.73 m² attenuation of eGFR progression at week 52 with roxadustat vs placebo (p<0.0001) and a 36 percent reduction in eGFR decline.

According to the authors, roxadustat demonstrated an acceptable CV profile vs placebo with HRs of 1.08 and 1.04 for MACE and MACE+, respectively, in the intention-to-treat population, and 0.99 and 0.98, respectively, in the subgroup of 3,431 patients with baseline eGFR >10 mL/min/1.73 m².

“Roxadustat patients had significantly longer MACE- and MACE+-free survival on treatment than placebo (p<0.0001),” they said.