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Abstract: PO2623

Results from a Phase 3 Study Comparing the Efficacy and Safety of Molidustat vs. Darbepoetin Alfa in Patients Receiving Hemodialysis and Treated with Erythropoiesis-Stimulating Agents (ESAs)

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan
  • Yamada, Takashi, Bayer Yakuhin Ltd, Osaka, Japan
  • Nobori, Kiyoshi, Bayer Yakuhin Ltd, Osaka, Japan
  • Matsuda, Yoshimi, Bayer Yakuhin Ltd, Osaka, Japan
  • Hayashi, Yasuhiro, Bayer Yakuhin Ltd, Osaka, Japan
  • Hayasaki, Takanori, Bayer Yakuhin Ltd, Osaka, Japan
  • Yamamoto, Hiroyasu, The Jikei University School of Medicine, Tokyo, Japan
Background

Molidustat is a novel inhibitor of hypoxia-inducible factor-prolyl hydroxylase under investigation as an alternative to ESAs for the treatment of renal anemia.

Methods

This 52-week, phase 3 randomized, active-controlled, double-blinded, double-dummy, parallel-group, multi-center study (NCT03543657) compared the efficacy and safety of molidustat with darbepoetin alfa in Japanese patients with end-stage kidney disease receiving hemodialysis and ESA treatment. The dose of oral molidustat (5–200 mg/day) or intravenous darbepoetin alfa (10–180 μg every 1 or 2 weeks) was adjusted to maintain hemoglobin (Hb) concentrations within the target range 10.0–12.0 g/dL. The primary variables were mean Hb level during evaluation period (Weeks 33–36) and its change from baseline.

Results

Of 229 patients randomized to molidustat (n=153) or darbepoetin alfa (n=76), 180 completed 52 weeks of treatment (n=115 and 65). Median treatment duration was 364 days with molidustat and 364 days with darbepoetin alfa. Baseline characteristics were generally well balanced between groups: patients’ mean age was 65.7, mean BMI was 22.5 and 61% were male. Mean baseline central Hb levels were 10.77 g/dL for molidustat and 10.84 g/dL for darbepoetin alfa. The mean (95% CI) for mean Hb level during the evaluation period were within the target range for both groups: 10.63 (10.42–10.84) g/dL with molidustat and 10.77 (10.59–10.95) g/dL with darbepoetin alfa. Noninferiority of molidustat to darbepoetin alfa for the change in mean Hb level from baseline to the evaluation period was established, with a margin of 1.0 g/dL (least square mean difference [95% CI] for molidustat vs darbepoetin alfa: -0.13 (-0.46–0.19] g/dL). There were no apparent between-group differences in incidence of treatment-emergent adverse events (TEAEs) (molidustat, 95.4%; darbepoetin alfa, 94.7%), serious TEAEs (24.2%; 18.4%), TEAEs with an outcome of death (1.3%; 2.6%) or AEs of special interest (4.6%; 3.9%).

Conclusion

In Japanese patients receiving hemodialysis and previously treated with ESAs, molidustat was noninferior to darbepoetin alfa for maintaining Hb levels, and no new safety concerns were observed.

Funding

  • Commercial Support