Kind Pharmaceutical presented positive results from four clinical trials of AND017, a novel hemoglobin elevating agent, for treating anemia associated with chronic kidney disease (CKD) at the American Society of Nephrology (ASN) Kidney Week 2024. The trials included studies in both non-dialysis dependent (NDD-CKD) and dialysis-dependent (DD-CKD) patients.
Phase 1 Trials: AU-001 and CN-101
The AU-001 trial, a double-blinded, placebo-controlled, first-in-human study, assessed the safety and pharmacokinetics of AND017 in healthy subjects. Results showed favorable linear oral pharmacokinetics with an elimination half-life (T1/2) between 11.9 and 19.7 hours in the single ascending dose (SAD) part (1 mg to 50 mg) and between 10.1 and 19.4 hours in the multiple ascending dose (MAD) part (4 mg to 30 mg QD for 10 days). Preliminary pharmacodynamic markers (EPO, Hb) were also observed. AND017 was safe and well-tolerated across all doses.
The CN-101 trial, a phase I, randomized, open-label, crossover study, evaluated the effect of food on the pharmacokinetics of AND017 in healthy Chinese subjects. The trial demonstrated that AND017, with its current formulation, can be administered with or without food, as the fed/fasted ratios for Cmax and AUC0-inf were within acceptable limits.
Phase 2 Trial in NDD-CKD: MN-201
The MN-201 trial was a phase II, randomized, double-blinded, placebo-controlled, dose-ranging study in the U.S. and China, involving 113 NDD-CKD patients. Participants were randomized to receive AND017 at 8 mg, 12 mg, or 16 mg three times weekly (TIW) or placebo. After five weeks, AND017-treated patients were re-randomized to TIW or once-weekly (QW) dosing regimens for an eight-week titration period.
Results showed that all AND017 dose groups had significantly higher hemoglobin (Hb) rise rates from baseline compared to placebo. The dose of AND017 and the rate of rise in Hb were linearly correlated. Hemoglobin levels were maintained within the target range (10.0-11.0 g/dL) in both TIW and QW dosing groups during the titration period. The treatment was generally safe and well-tolerated, with a safety profile similar to placebo.
Phase 2 Trial in DD-CKD: MN-202
The MN-202 trial was a phase II, randomized, open-label, active-controlled study in the U.S. and China, assessing AND017 in dialysis-dependent patients with end-stage kidney disease (ESKD). Patients were randomized to AND017 10 mg TIW, AND017 16 mg QW, or erythropoietin stimulating agents (ESA). Doses were adjusted to target Hb ranges within 11.0-11.0 g/dL in the U.S. and 10.0-12.0 g/dL in China.
Both AND017 groups (10 mg TIW and 16 mg QW) demonstrated non-inferiority to ESA in maintaining Hb levels within the target range during the 20-week treatment period. The safety profile was also favorable, with the only treatment-related treatment emergent adverse event (TEAE) reported as hyperkalemia (1 patient in the AND017 10 mg TIW group).
Clinical Significance
"AND017 demonstrated adequate safety and effectively increased and maintained hemoglobin levels in the 10.0-11.0 g/dL range in two Phase II studies involving both NDD and DD CKD patient populations. Efficacy and safety will be further assessed in Phase III trials," said Pablo E. Pergola, MD, Ph.D., an expert in nephrology and the director of the Clinical Advancement Center, PLLC, a wholly-owned subsidiary of Renal Associates.
Qi Zhu, MD, the CMO of Kind Pharmaceutical, added, "The longer interval dosing could be one of the keys to mitigate MACE issue, which plagued the previous clinical trials for anemia in NDD CKD. We are willing to tackle this tough problem in phase III trials."
About Anemia in CKD
Anemia is a common complication of chronic kidney disease (CKD), affecting a significant portion of the population. In the United States, approximately 14% of adults have CKD, while in China, the prevalence is around 8%. Anemia in CKD can increase the risk of cardiovascular complications, such as heart failure and stroke, and increase morbidity and mortality.
