Kidney Week

Abstract: TH-PO898

Safety and Efficacy of AND017, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), in Patients with Nondialysis-Dependent CKD (NDD-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

• Zhu, Yusha, Kind Pharmaceuticals LLC, Redwood City, California, United States

Yusha Zhu, MD, PhD

• Zuo, Li, Peking University People's Hospital, Beijing, China

Li Zuo, MD

• Ding, Xiaoqiang, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China

Xiaoqiang Ding

• Wilson, Suzanne, Kind Pharmaceuticals LLC, Redwood City, California, United States

Suzanne Wilson

• Du, Ping, Kind Pharmaceuticals LLC, Redwood City, California, United States

Ping Du

• Zhu, Qi, Kind Pharmaceuticals LLC, Redwood City, California, United States

Qi Zhu, MD

• Block, Geoffrey A., US Renal Care, Dallas, Texas, United States

Geoffrey A. Block, MD, FASN

• Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States

Pablo E. Pergola, MD, PhD

Background

AND017, a novel HIF-PHI, was investigated in a Phase II study in patients with NDD-CKD in the US and China (NCT05035641).

Methods

Patients with NDD-CKD and hemoglobin (Hb) ≥7.5 and <10.0 g/dL were randomized at a 1:1:1:1 ratio to AND017 8 mg, 12 mg, 16 mg or placebo three times weekly (TIW) during the first 5-weeks treatment (Fixed-dose Period, no dose adjustment allowed). At the end of the Fixed-dose period (Week 6), patients who met the pre-defined criteria were re-randomized at a ratio of 1:1 to continue the TIW dosing schedule or switch to a once-weekly (QW) dosing schedule and entered the 8-week Titration Period. During this period, the doses of the study drug were adjusted to maintain Hb within the range of 10.0-11.0 g/dL inclusive.
The primary objectives were to evaluate the safety and efficacy of AND017 by assessing the rate of rise in Hb at Week 6.

Results

A total of 113 patients were enrolled: placebo (28), 8 mg (28), 12 mg (29), and 16 mg (28). Treatment-emergent adverse events occurred in 69.41% in the pooled AND017 group versus 64.29% in the placebo group while treatment-related adverse events occurred in 11.76% in the pooled AND017 group versus 3.57% in the placebo group. A total of 6 patients from AND017 dose groups experienced serious adverse events (SAEs), none of which were assessed as related to the study drug.
Compared to the placebo group, the mean rate of rise in Hb (g/dL/week) from baseline to Week 6 was significantly higher in all the AND017 dose groups (p<0.0001). Change from baseline in Hb at Week 6 was 1.44 g/dL, 2.03 g/dL, 2.51 g/dL in AND017 8 mg, 12 mg, and 16 mg group, respectively, and -0.21 g/dL in the placebo. The cumulative response rates (Hb ≥10.0 g/dL and increase from baseline ≥1.0 g/dL during the entire treatment period) were higher in all AND017 dose and dosing frequency groups, 100% and 90% for the pooled AND017 TIW group and QW group, respectively, compared to 40% in the placebo.

Conclusion

AND017 was safe and well tolerated in patients with NDD-CKD and anemia. AND017 effectively increased Hb level in a dose-dependent manner starting at 8 mg TIW within the first 5-week Fixed-dose period and maintained Hb within 10.0-11.0 g/dL at both TIW and QW dosing frequency in the following 8-week Titration period.