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Abstract: TH-PO1185

Phase 3 Study to Compare the Efficacy and Safety of Enarodustat (JTZ-951), an Oral HIF-PH Inhibitor, with Darbepoetin Alfa in Anemic Patients with CKD Not Requiring Dialysis

Session Information

Category: Anemia and Iron Metabolism

  • No subcategory defined

Authors

  • Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan
  • Matsui, Atsushi, Japan Tobacco Inc., Tokyo, Japan
  • Miyazawa, Yuya, Japan Tobacco Inc., Tokyo, Japan
  • Koretomo, Ryosuke, Japan Tobacco Inc., Tokyo, Japan
Background

This phase 3 study was conducted to verify the efficacy (non-inferiority to darbepoetin alfa (DA)) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis in randomized, open-label, parallel-arm comparison manner for 24 weeks.

Methods

Patients were respectively randomized in 1:1 ratio to receive either enarodustat orally once daily or DA subcutaneously every 2 or 4 weeks. The doses were adjusted every 4 weeks to maintain Hb levels within a target range (10-12 g/dL). The primary endpoint was difference in mean Hb level between arms during the evaluation period defined as Week 20-24 (non-inferiority margin: -0.75 g/dL). Other assessments included proportion of patients whose Hb level was within the target range, iron-related parameters, renal function-related parameters, and NT-pro BNP.

Results

216 patients were randomized to receive either enarodustat (n=107) or DA (n=109). The mean Hb level of each arm during the evaluation period was 10.96 g/dL (95% CI: 10.84, 11.07) with enarodustat arm and 10.87 g/dL (95% CI: 10.75, 10.99) with DA arm. The difference between arms in the mean Hb level was 0.09 g/dL (95% CI: -0.07, 0.26), confirming the non-inferiority to DA. Proportions of patients whose Hb level was within the target range during the evaluation period were 89.6% in enarodustat arm and 90.6% in DA arm. Increase of TIBC and decrease of hepcidin were observed in enarodustat arm. No apparent difference between arms in the incidence of AEs including CV events and hypertension-related events were observed. There were no negative effects of enarodustat on NT-pro BNP or renal function-related parameters.

Conclusion

Enarodustat, administered orally, was as effective as DA, administered subcutaneously, in maintaining Hb levels in Japanese anemic patients with CKD not requiring dialysis. No new safety concerns were identified when compared with DA.

Funding

  • Commercial Support – Japan Tobacco Inc.