Maze Therapeutics has announced positive results from its Phase I clinical trial evaluating MZE829, an oral small molecule inhibitor of apolipoprotein L1 (APOL1), as a potential treatment for APOL1 kidney disease (AKD). The randomized, placebo-controlled, single and multiple ascending dose study in 111 healthy volunteers demonstrated that MZE829 was well-tolerated and exhibited favorable pharmacokinetics, paving the way for a Phase II trial in AKD patients slated for the first quarter of 2025.
Phase I Trial Details
The Phase I trial was designed as a first-in-human study to assess the safety, pharmacokinetics (PK), food effect, and potential drug interactions of MZE829. Participants were administered single doses up to 480mg and multiple doses up to 350mg. The results indicated that MZE829 was well-tolerated across all tested doses, with no serious adverse events reported. All treatment-related adverse events were mild.
Pharmacokinetic Profile
Pharmacokinetic analysis revealed dose-proportional exposure and low variability, suggesting predictable drug behavior. The half-life of approximately 15 hours supports the feasibility of once-daily oral administration, a significant advantage for patient compliance. Furthermore, MZE829 showed no concerning interactions with standard-of-care medications for AKD, such as cyclosporine and tacrolimus, indicating its potential for use in combination therapies.
Clinical Significance and Next Steps
APOL1 kidney disease disproportionately affects individuals of West African descent and is linked to genetic variants G1 and G2 of the APOL1 gene, which increase the risk of progressive kidney diseases. Currently, treatment options are limited, highlighting the unmet need for targeted therapies.
"We are very pleased with the positive outcome of our Phase I trial of MZE829, demonstrating its tolerability and establishing the dosing regimen that we plan to take into our Phase II trial in patients with AKD," said Harold Bernstein, M.D., Ph.D., president of research and development and chief medical officer of Maze Therapeutics. "Based on its mechanism targeting APOL1, as well as genetics data derived through our Compass platform, we believe that MZE829 has the potential to address a large population of patients with AKD."
The upcoming Phase II trial will further evaluate the efficacy and safety of MZE829 in AKD patients, with a Phase III trial planned to assess a variety of clinical phenotypes and disease severities based on proteinuria levels, utilizing an open-label basket design.
