Kind Pharmaceutical presented positive results from four clinical trials of AND017, a novel hemoglobin elevating agent, at the American Society of Nephrology (ASN) Kidney Week 2024 in San Diego. The trials investigated AND017's efficacy and safety in treating anemia associated with both non-dialysis dependent chronic kidney disease (NDD-CKD) and dialysis-dependent chronic kidney disease (DD-CKD).
Phase I Trials: AU-001 and CN-101
The AU-001 trial, a double-blinded, placebo-controlled, first-in-human study in healthy subjects in Australia, demonstrated that AND017 has favorable linear oral pharmacokinetics. The elimination half-life (T1/2) ranged from 11.9 to 19.7 hours for single ascending doses (1 mg to 50 mg) and 10.1 to 19.4 hours for multiple ascending doses (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 in China, examined the effect of food on AND017's pharmacokinetics. Results indicated that AND017 can be administered with or without food, as the fed/fasted ratio of geometric mean of Cmax was 79.61% (90% CI: 73.40, 86.34) and the fed/fasted ratio of geometric mean of AUC0-inf was 99.93% (90% CI: 96.31, 103.68).
Phase II Trials: MN-201 and MN-202
The MN-201 trial was a Phase II, randomized, double-blinded, placebo-controlled, dose-ranging study conducted in the U.S. and China. A total of 113 NDD-CKD patients were randomized to receive AND017 at 8 mg, 12 mg, or 16 mg three times weekly (TIW), or placebo. After 5 weeks, AND017-treated patients were re-randomized to TIW or once weekly (QW) dosing for an 8-week titration period. At Week 6, all AND017 dose groups showed significantly higher hemoglobin (Hb) rise rates from baseline compared to placebo. The Hb levels were maintained within the target range (10.0-11.0 g/dL) in both TIW and QW dosing groups during the titration period. Treatment emergent adverse events (TEAEs) were similar between AND017 (69.4%) and placebo (64.3%) groups. The trial demonstrated that AND017 was safe and effectively increased Hb levels in a dose-dependent manner.
The MN-202 trial was a Phase II, randomized, open-label, active-controlled study in dialysis-dependent ESKD patients in the U.S. and China. Patients were randomized to AND017 10 mg TIW, AND017 16 mg QW, or erythropoietin stimulating agents (ESA). Both AND017 groups demonstrated non-inferiority to ESA in maintaining Hb levels within the target range (11.0-11.0 g/dL in U.S. and 10.0-12.0 g/dL in China) during the 20-week treatment period. TEAEs occurred in 78.4% of AND017-treated patients and 66.1% of ESA-treated patients. Hyperkalemia was the only treatment-related TEAE reported in more than one AND017-treated patient (1.7%).
Clinical Implications
"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 Dr. Pablo E. Pergola, an expert in nephrology.
According to Dr. Qi Zhu, CMO of Kind Pharmaceutical, the longer interval dosing option with AND017 could be key to mitigating major adverse cardiovascular events (MACE), a problem encountered in previous anemia trials. The company plans to address this in Phase III trials.
Anemia is a common complication of chronic kidney disease, affecting approximately 14% of adults in the United States and 8% in China. It increases the risk of cardiovascular complications and mortality. AND017 represents a potential new treatment option for this patient population.
AND017 has also received Orphan Drug Designation from the FDA for the treatment of sickle cell disease.
