Abstract: SA-PO225
Two Phase 3, Multicenter, Randomized Studies of Intermittent Oral Roxadustat in Anemic CKD Patients on (PYRENEES) and Not on (ALPS) Dialysis
Session Information
- Anemia and Iron Metabolism: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 202 Anemia and Iron Metabolism: Clinical
Authors
- Esposito, Ciro, ICS Maugeri SpA, University of Pavia, Pavia, Italy
- Csiky, Botond, FMC Dialysis Center, Pecs, Hungary
- Tataradze, Avtandil, National Center of Urology, Tbilisi, Georgia
- Reusch, Michael, Astellas Pharma Europe B.V., Leiden, Netherlands
- Han, Cong, Astellas, Northbrook, Illinois, United States
- Sulowicz, Wladyslaw, Dept. of Nephrology, Jagiellonian University, Krakow, Poland
Background
Roxadustat is an oral HIF-PHI in late-stage development for treatment of CKD anemia.
Methods
Two phase 3 European studies enrolled non–dialysis-dependent (NDD; ALPS) and dialysis-dependent (DD; PYRENEES) patients with CKD anemia. In the double-blind NDD study, patients with hemoglobin (Hb) ≤10 g/dL not treated with erythropoiesis-stimulating agents (ESAs) were randomized (2:1) to oral 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 oral 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 study), and mean monthly IV iron use through Week 36 (DD study). 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 in 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 in 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 in NDD patients, and hypertension, arteriovenous fistula thrombosis, headache, and diarrhea in DD patients. Roxadustat safety data will be integrated across all trials.
Conclusion
Roxadustat was effective in achieving and maintaining Hb levels compared with placebo and ESA in NDD- and DD-CKD patients.
Funding
- Commercial Support –