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Abstract: TH-PO225

Enarodustat (JTZ-951), an Oral HIF-PH Inhibitor, Elevates and Maintains Hemoglobin Levels over 30 Weeks in Japanese Anemic Patients with CKD Not on Dialysis

Session Information

Category: Anemia and Iron Metabolism

  • 202 Anemia and Iron Metabolism: Clinical

Authors

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

The dose response in Hb and safety of enarodustat administered for 6 weeks in anemic patients with CKD not on dialysis (ND-CKD) was assessed in a placebo-controlled, randomized, double-blind manner (period I). In addition, the maintenance dosage and safety of long-term treatment with enarodustat was assessed in an open-label manner for 24 weeks (period II).

Methods

ESA naïve subjects (G1) and subjects receiving a stable dose of ESAs (G2), who have protocol specified Hb criteria, were respectively randomized in 1:1:1:1 ratio to receive either enarodustat doses of 2, 4, 6 mg or placebo once daily. Subjects, who completed the period I and were eligible for the period II, received long-term treatment with enarodustat that was adjusted in the range of 2 to 8 mg to maintain Hb in a target range of 10.0-12.0. Use of IV iron was prohibited by the end of period I.

Results

The weekly Hb elevation rate in G1 was significantly increased with dose. In G2, the changes in Hb from baseline at endpoint were also increased with dose. In period II, the proportion of subjects who maintained Hb level within the target range at end of treatment in G1 and G2 were 71.4% and 83.1%, respectively. While Hb levels over the course of Period II stayed in a target range, more than 70% subjects experienced ≤ 1 dose adjustment during the period II. Median hepcidin and ferritin levels were decreased across all the enarodustat arms during period I in contrast with increase in TIBC levels. These parameters remained stable during period II. Enarodustat was generally well tolerated.

Conclusion

Enarodustat corrected and maintained Hb levels in anemic patients with ND-CKD with minimum dose adjustment requirement. Furthermore, better iron availability and utilization by enarodustat are suggested to be contributed to erythropoietic responses, which is expected to provide alternative and more physiologic treatment option to ESA for anemic patients with CKD. The efficacy and safety compared with ESA and long-term studies are being examined in phase 3 studies.

Funding

  • Commercial Support