Maze Therapeutics (Nasdaq: MAZE), based in South San Francisco, reported topline data from its Phase II HORIZON trial of MZE829, an oral APOL1 inhibitor, in patients with APOL1-mediated kidney disease. According to the company, treatment with MZE829 resulted in a 35.6% mean reduction in urinary albumin-to-creatinine ratio from baseline at week 12 across 12 evaluable patients, with 50% of patients achieving at least a 30% uACR reduction. Maze said it plans to advance MZE829 into a pivotal program.
The HORIZON trial used an open-label basket design enrolling patients with the APOL1 high-risk genotype across diabetic and non-diabetic AMKD populations, including patients with biopsy-confirmed focal segmental glomerulosclerosis. Of 15 enrolled patients, 12 met per-protocol compliance thresholds for efficacy evaluation. Most patients were sub-nephrotic at baseline, with 10 having uACR between 300 and 1,000 mg/g. In the FSGS subgroup, the company reported a 61.8% mean uACR reduction; in non-diabetic AMKD patients, the mean reduction was 48.6%. Among diabetic AMKD patients, five were evaluable, with two achieving at least a 30% uACR reduction. On safety, no serious adverse events or severe treatment-related adverse events were observed across the 15-patient safety population. The most common treatment-related adverse events were headache and diarrhea, each occurring in two patients. One patient discontinued early due to mild nausea.
The trial's primary endpoints were safety and tolerability, with uACR reduction as a secondary endpoint. The company did not disclose specific dosing regimens, stating only that MZE829 was evaluated "across all doses." All patients were required to be on stable background chronic kidney disease therapies, including SGLT2 inhibitors and GLP-1 receptor agonists, for at least eight weeks prior to treatment. The data are based on 12 evaluable patients at a single 12-week timepoint in an open-label setting without a placebo comparator, which limits interpretation of treatment effect. Pharmacokinetic data, a secondary endpoint, were not reported. Longer-term durability of uACR reductions and effects on kidney function decline remain unknown.
MZE829 is described by the company as a dual-mechanism APOL1 inhibitor that targets both pore formation and channel function in podocytes. No other APOL1 inhibitor has reported Phase II efficacy data in a genetically defined AMKD population, according to the company, though inaxaplin (Vertex Pharmaceuticals) has been evaluated in APOL1-mediated FSGS. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.
Spot something wrong? Report an issue with this article