Kidney Week

Abstract: TH-PO1151

Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Conversion Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan

Session Information

• Late-Breaking Clinical Trials Posters
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• No subcategory defined

Authors

• Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan

Tadao Akizawa,

• Iwasaki, Manabu, Yokohama City University, Yokohama, Japan

Manabu Iwasaki,

• Yamaguchi, Yusuke, Astellas Pharma Inc., Tokyo, Japan

Yusuke Yamaguchi,

• Majikawa, Yoshikatsu, Astellas Pharma Inc., Tokyo, Japan

Yoshikatsu Majikawa,

• Reusch, Michael, Astellas Pharma Europe B.V., Leiden, Netherlands

Michael Reusch,

Background

Roxadustat, an oral HIF-PHI, is in late-stage development for treatment of CKD anemia. This phase 3 study evaluated non-inferiority of roxadustat efficacy to darbepoetin alfa (DA) as treatment of CKD anemia on hemodialysis (HD).

Methods

Multicenter, 24-week, Japanese study of CKD anemia patients on HD for ≥12 weeks and treated with ESA. Patients were randomized to roxadustat (70mg and 100mg) three times weekly or DA (10-60μg) once weekly; dose was adjusted to maintain Hb at 10-12g/dL. Primary endpoint was change of average Hb from baseline to Weeks 18-24 (△Hb_18-24). Roxadustat efficacy was confirmed if the 95% CI of average Hb at Weeks 18-24 was within 10-12g/dL; non-inferiority to DA was confirmed if the lower limit of the 95% CI of the difference between roxadustat and DA was above –0.75g/dL. Secondary endpoints were average Hb at Weeks 18-24, proportion of patients with Hb of 10-12g/dL at Weeks 18-24 (maintenance rate), and iron parameters (ie, serum iron, ferritin, TSAT, transferrin, and TIBC). Safety was assessed as occurrence of adverse events (AEs) including ophthalmological examination (color fundus photography and optical coherence tomography [OCT]).

Results

303 patients were randomized to roxadustat (n=151) or DA (n=152). The average Hb at Weeks 18-24 was 10.99 g/dL (95% CI: 10.88, 11.10) with roxadustat, confirming its efficacy. The difference between roxadustat and DA in △Hb_18-24 was –0.02g/dL (95% CI: –0.18, 0.15), confirming non-inferiority of roxadustat to DA. Maintenance rate of target Hb in patients with ≥1 Hb value at Weeks 18-24 was 95.2% (roxadustat) and 91.3% (DA). With roxadustat, serum iron, ferritin, and TSAT showed no remarkable change; transferrin and TIBC increased through Week 4 and then remained stable. No remarkable changes in iron parameters occurred with DA. The most common AEs in both groups were nasopharyngitis, shunt stenosis, diarrhea, contusion, and vomiting. New/worsening retinal hemorrhage occurred in 32.4% (roxadustat) and 36.6% (DA) of patients; no clinically meaningful change in retinal thickness by OCT were observed over time between groups.

Conclusion

Roxadustat maintained target Hb in HD patients and its efficacy was non-inferior to DA. AEs were consistent with previous reports.

Funding

• Commercial Support – Astellas Pharma Inc