Kidney Week

Abstract: TH-PO905

Impact of Roxadustat Kinetic Pharmacodynamics on Starting Dosage for Anemia in Dialysis-Dependent (DD) and Nondialysis-Dependent (NDD) Patients with CKD

Session Information

• Anemia and Iron Metabolism
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Deng, Chenhui, Clinical Pharmacology Department, Linking Truth Technology Co., Ltd, Beijing, Beijing, China

Chenhui Deng, PhD

• Liu, Ping, Clinical Pharmacology Department, Linking Truth Technology Co., Ltd, Beijing, Beijing, China

Ping Liu, PhD

• Wu, Yiqing, Medical Affairs, FibroGen (China) Medical Technology Development Co., Ltd., Beijing, Beijing, China

Yiqing Wu, DrMed

Background

We evaluated the impacting factors on roxadustat pharmacodynamics, and simulated relevant dosing regimens based on the established kinetic-pharmacodynamic (K-PD) model to support the starting dose optimization in Chinese CKD anemia patients.

Methods

The analysis included 9964 hemoglobin (Hb) data from 992 Chinese patients in 6 Phase 2/3/4 clinical studies. Based on the established K-PD model, Hb levels in these patients at standard or 1–step lower starting dosing regimen were simulated following 52 weeks of three times weekly administration. Dose adjustment was allowed based on Hb levels at Week 4 and later to maintain Hb levels within 10.5-12.0 g/dL.

Results

The Hb profiles in CKD anemia patients were well described with a cell lifespan model. Body weight, subject type (DD/NDD), and prior erythropoietin (EPO) dose (≥ or <10,000 IU/wk) were significant covariates for roxadustat dose at half of the maximum stimulation (ED₅₀); the effect of CKD stage (3&4) on ED₅₀ in 1 Phase 4 study (NDD) was also included in the final model. For NDD CKD stage 3&4 patients, erythropoiesis-stimulating agent (ESA)-naïve DD patients, and ESA-treated DD patients with prior EPO dose <10,000 IU/wk, following the 1–step lower starting dose, adequate efficacy (10.5 g/dL≤ Hb <12.0 g/dL) could still be maintained and proportions of patients with high Hb levels (Hb ≥13.0 & Hb ≥12.0 g/dL) could be further reduced compared to the standard starting dose. For NDD CKD stage 5 patients, at the standard starting dose, a higher proportion of patients had an increase in Hb levels of 1-2 g/dL within the first 4 weeks without obvious increase in proportions of patients with high Hb levels, compared to the 1–step lower starting dose. For ESA-treated DD patients with prior EPO dose ≥10,000 IU/wk, at the standard starting dose, a higher proportion of patients maintained adequate efficacy for the first 8 weeks without obvious increase in proportions of patients with high Hb levels, compared to the 1–step lower starting dose.

Conclusion

For NDD CKD stage 5 patients and ESA-treated DD patients with prior EPO dose ≥10,000 IU/wk, the standard starting dose can be maintained. For NDD CKD stage 3&4 patients, ESA-naïve DD patients, and ESA-treated DD patients with prior EPO dose <10,000 IU/wk, the 1–step lower starting dose may be considered.

Funding

• Commercial Support – FibroGen (China) sponsored this analysis