Abstract: SA-PO0271
Quantitative Pharmacology of AND017, a Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), to Support Phase 3 Dose Selection in Anemia Due to CKD
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Zhu, Yusha, Kind Pharmaceuticals LLC, Redwood City, California, United States
- Xie, Haitang, Wannan Medical College Shool of Pharmacy, Wuhu, Anhui, China
- Sun, Hua, Wannan Medical College Shool of Pharmacy, Wuhu, Anhui, China
- Liu, Zhiwei, Wannan Medical College Shool of Pharmacy, Wuhu, Anhui, China
- Li, Yiming, Wannan Medical College Shool of Pharmacy, Wuhu, Anhui, China
- Chen, Youjun, Wannan Medical College Shool of Pharmacy, Wuhu, Anhui, China
- Du, Ping, Kind Pharmaceuticals LLC, Redwood City, California, United States
- Li, Xiaolu, Kind Pharmaceuticals LLC, Redwood City, California, United States
- Zhu, Qi, Kind Pharmaceuticals LLC, Redwood City, California, United States
Background
AND017 is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI) developed for the treatment of anemia due to CKD. Two Phase I studies among healthy participants, and two Phase II studies among patients of renal anemia have been completed for AND017. Before the designing of Phase III studies of AND017, a PBPK/PD model was developed to support the dose selection by PK-Sim® and MoBi®.
Methods
The PBPK/PD model includes 18 systemic physiological compartments and 4 sub-compartments to simulate the PK process. Drug-specific parameters were optimized by the Monte Carlo algorithm. The PBPK model was trained and validated by data from the Phase I study of AND017 and extrapolated to the CKD population. The PD model described the in vivo process from HIF-PHD inhibition to hemoglobin (Hb) increase by AND017, with the data derived from two Phase II studies.
Results
Model simulations of AND017 showed that the total plasma clearance was 0.18, 0.23, and 0.28 mL/min/kg in the healthy participants, NDD-CKD patients, and DD-CKD patients, respectively. For drugs like AND017 that primarily eliminated through non-renal pathways, a higher clearance rate leads to reduced drug exposure in the patient’s body. Model simulations of PK parameters following a 10 mg dose of AND017 showed that drug exposure was 0.80 times and 0.62 times that of healthy individuals in NDD-CKD patients and DD-CKD patients, respectively.
PK/PD behavior under different dosing regimens (8 mg, 12 mg, 16 mg three times weekly (TIW) for NDD-CKD and 10 mg TIW for DD-CKD) were simulated to support the selection of the starting doses and dose adjustment strategies for Phase III studies. At 8 mg TIW in NDD-CKD patients and 10 mg TIW in DD-CKD patients, the Hb levels in both demonstrated good similarity by both PK and PD outcomes.
After 4 weeks of treatment, once Hb levels reached or were maintained above the target threshold, the dosing frequency was switched from TIW to once weekly (QW) (simulated at different doses). A slightly higher QW dose demonstrated a favorable trend in maintaining Hb levels.
Conclusion
Given the PK differences between NDD-CKD and DD-CKD patients, the starting doses of AND017 will be 8 mg TIW and 10 mg TIW, respectively. Once Hb levels reach the target range, dosing may be switched from TIW to QW at a slightly higher dose.