engleski

Two phase 3, multicenter, randomized studies of intermittent oral roxadustat in anemic CKD patients on (PYRENEES) and not on (ALPS) dialysis

Goals: Roxadustat is an oral HIF-PHI in late-stage development for treatment of CKD anemia. Two phase 3 European studies enrolled non–dialysis-dependent (NDD) and dialysis-dependent (DD) patients with CKD anemia to assess whether roxadustat was effective in correcting and maintaining hemoglobin (Hb) levels, compared with placebo (NDD) and ESA (DD). Materials and Methods: In the double-blind NDD study, patients with Hb ≤10 g/dL not treated with erythropoiesis-stimulating agents (ESAs) were randomized (2:1) to roxadustat or placebo for 52-104 weeks. In the open-label DD study, stable hemodialysis or peritoneal dialysis patients with Hb 9.5-12 g/dL treated with ESAs were randomized (1:1) to roxadustat or ESAs for 52-104 weeks. Primary endpoints were change of average Hb levels at Weeks 28-52 from baseline. Secondary endpoints included change of average low-density lipoprotein cholesterol (LDL) at Weeks 12-28 from baseline, time to use of rescue therapy (ie, transfusion, ESA, IV iron ; NDD), and mean monthly IV iron use through Week 36 (DD). Occurrence of adverse events (AEs) was also assessed. Results: The NDD study randomized 594 patients to roxadustat (n=391) or placebo (n=203) ; the DD study randomized 836 patients to roxadustat (n=415) or ESA (n=421). Mean (SD) change of average Hb levels at Weeks 28-52 from baseline was 1.988 (0.953) for roxadustat and 0.406 (0.979) for placebo (P<0.001) in NDD patients and 0.396 (0.773) for roxadustat and 0.183 (0.860) for ESA in DD patients (P<0.001). The LS mean difference (95% CI) in LDL was -0.701 (-0.83, -0.57 ; P<0.001) mmol/L vs placebo in NDD patients and -0.377 (-0.451, -0.304 ; P<0.001) mmol/L vs ESA in DD patients. In NDD patients, roxadustat was superior to placebo regarding time to use of rescue therapy (hazard ratio [95% CI], 0.238 [0.17, 0.33] ; P<0.001). In DD patients, roxadustat was superior to ESA regarding mean monthly IV iron use (LS mean difference [95% CI], -31.9 [-41.4, -22.4] ; P<0.001). Common AEs in both treatment groups were ESRD, hypertension, peripheral edema, and decreased GFR (NDD) and hypertension, arteriovenous fistula thrombosis, headache, and diarrhea (DD). Conclusions: Roxadustat was effective in correcting and maintaining Hb levels compared with placebo and ESA in NDD- and DD-CKD patients, respectively.

Roxadustat ; Renal Anemia, CKD

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